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Background: To study the effects of various courses of dexamethasone (DEX) combined with 5-HT3 receptor antagonists (RA) and NK-1 RA in suppressing high-grade nausea and vomiting (CINV) caused by anthracycline and cyclophosphamide chemotherapy regimens (AC or EC) in breast cancer (BC) patients., Patients and Methods: A prospective study was performed with 252 BC patients who received AC between January, 2019 and June, 2022 in our hospital. Patients were randomly separated into control Group (N = 130) who received DEX 12 mg on day 1 and 8 mg per dose on day 2-4 and observation group (N = 122) treated with DEX 5 mg per dose on days 1-4. The response was monitored. Primary study endpoint was complete resolution (CR) of patients nausea or vomiting; secondary study endpoints included acute CR and delayed CR; and complete control (CC), acute CC, delayed CC, and safety., Results: All patients underwent six rounds of chemotherapy, and no difference was found in the clinical data. CR of acute/delayed phase was (94.3%/88.5%, P > 0.05), (89.3%/90.8%, P > 0.05); total CR was (80.3%/81.5%, P > 0.05); CC was (56.6%/59.2%, P > 0.05), (64.8%/67.7%, P > 0.05); total CR was (48.4%/53.1%, P > 0.05)., Conclusions: The preventive antiemetic effects of NEPA, a fixed-dose combination of netupitant and palonosetron combined with DEX 5 mg per dose on days 1-4, can be similar to DEX 12 mg on day 1 and 8 mg per dose on days 2-4, low-dose hormone with better safety, which is beneficial., Competing Interests: Declarations. Ethics approval and consent to participate: The current study was approved by the Ethics Committee of The 1st Affiliated Hospital of Wenzhou Medical University (ethic code: KY2022-R022) and complied with the guidelines outlined in the declaration of Helsinki. The written consent was received from all the participants. Consent for publication: Not applicable. Conflict of interest: The authors state that there are no financial, personal, or professional Conflict of interest that may hinder this work., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists including ondansetron, tropisetron, dolasetron, palonosetron, granisetron, and ramosetron are commonly used to prevent and treat nausea and vomiting. Most of these medications are at least partially metabolized via the highly polymorphic CYP2D6 enzyme, resulting in variations of metabolism among individuals. Current (2017) international prescribing guidelines for ondansetron/tropisetron use according to genotype provide recommendations for CYP2D6 ultrarapid metabolizers but not intermediate or poor metabolizers. However, multiple studies have been conducted since this guideline was published. This review evaluated all available evidence of an association between CYP2D6 genotype and 5-HT 3 receptor antagonist outcomes, including in patients who are CYP2D6 intermediate/poor metabolizers and pediatric-specific studies. In this review, we confirm that CYP2D6 genotype impacts ondansetron response in a postoperative nausea and vomiting setting, which was supported by a meta-analysis. We also highlight the heterogeneity and limitations of included studies as well as provide future directions for pharmacogenomics research., (© 2025 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Olanzapine is an atypical antipsychotic drug used for chemotherapy-induced nausea and vomiting. It is particularly effective in preventing delayed nausea and vomiting induced by highly emetogenic chemotherapy (HEC). However, it has side effects, such as hyperglycemia and somnolence, the efficacy and safety of adding olanzapine to triplet antiemetic therapy (5-HT 3 receptor antagonist, NK 1 receptor antagonist, and dexamethasone) must be verified., Methods: We performed a systematic review and meta-analysis to compare the effectiveness of olanzapine combined with triplet antiemetic therapy and triplet antiemetic therapy in preventing nausea and vomiting for HEC. We set five items (hyperglycemia, prevention of vomiting, prevention of nausea, adverse events, and cost (drug costs)) as outcomes and conducted a systematic review., Results: Five randomized controlled trials was extracted and they showed that the addition of olanzapine was effective in control of nausea and vomiting, especially in the delayed phase. Complete response of acute and delayed phase were significantly higher in the olanzapine group. Risk difference was - 0.14 [95% CI - 0.26, - 0.03; p = 0.02] and - 0.14 [95% CI - 0.19, -0.09; p < 0.00001], respectively. Additionally, we evaluated hyperglycemia and somnolence, which are typical side effects of olanzapine. However, the incidence of grade ≥ 2 was low in both events, and there was no significant difference between olanzapine and control groups., Conclusions: Adding olanzapine to triplet antiemetic therapy is useful in preventing nausea and vomiting induced by HEC and there would be minimal adverse effects from the combination use., Competing Interests: Declarations. Conflicts of interest: Michiyasu Murakami received honoraria from Taiho Pharmaceutical Co. Ltd. Kazuhisa Nakashima received honoraria from Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., AstraZeneca K.K., and Eli Lilly Japan K.K. Junichi Nishimura received honoraria from Taiho Pharmaceutical Co. Ltd. Eriko Satomi received honoraria from Shionogi & Co. Ltd. Masayuki Takeda received honoraria from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., and Bayer. Narikazu Boku received honoraria from Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Eli Lilly Japan K.K. Koji Matsumoto received honoraria from MSD K.K., Kyowa Kirin Co., Ltd., and Chugai Pharmaceutical Co., Ltd., as well as research funding from Daiichi Sankyo Co., Ltd., MSD K.K., Gilead Sciences, Inc., and Eli Lilly Japan K.K. Nobuyuki Yamamoto received honoraria from MSD K.K., Accuray Japan K.K., AstraZeneca K.K., Abbvie Inc., Amgen Inc., Ono Pharmaceutical Co., Ltd., Guardant Health Japan Corp., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Chugai Foundation for Innovative Drug Discovery Science, Lao Tsumura Co., Ltd., Terumo Corporation, Eli Lilly Japan K.K., Nippon Kayaku Co., Ltd., Novartis AG, Pfizer Global Supply Japan Inc., Merck Biopharma Co., Ltd, Pfizer Global Supply Japan Inc., Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., and USACO Corporation, as well as legal fees in case of iawsuit from Taiho Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan, Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Nippon Kayaku Co., Ltd., Prime Research Institute for Medical RWD, Inc., AstraZeneca K.K., and A2 Healthcare Corporation. Takako Eguchi Nakajima received research funding from KBBM, Inc. and Takeda Pharmaceutical Co., Ltd. Ethical approval: Not applicable. Informed consent: Formal consent was not required for this type of study. Consent to participate: Not applicable. Consent for publication: All authors consented to the publication of this study., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Palonosetron, a second-generation 5-HT 3 receptor antagonist (5-HT 3 RA), is more effective than first-generation 5-HT 3 RA. Several studies have investigated whether dexamethasone (DEX), when combined with palonosetron as a 5-HT 3 RA, can be spared in the delayed phase after moderately emetogenic chemotherapy (MEC). In this systematic review, we aimed to determine which between 1- and 3-day DEX administration, when combined with palonosetron, is more useful in patients receiving MEC., Methods: The PubMed, Cochrane Library, and Ichushi-Web databases were searched for relevant studies published between 1990 and 2020. We included studies that compared the efficacy of 1- and 3-day DEX administration in preventing nausea and vomiting associated with MEC. Outcomes were "prevention of vomiting (complete response rate and no vomiting rate)," "prevention of nausea" (complete control rate, total control rate, no nausea rate, and no clinically significant nausea rate)" in the delayed phase, "prevention of blood glucose level elevation," and "prevention of osteoporosis.", Results: Eight studies were included in this systematic review. The no vomiting rate was significantly higher in the 3-day DEX group than in the 1-day DEX group. However, the other efficacy items did not significantly differ between the two groups. Meanwhile, insufficient evidence was obtained for "prevention of blood glucose level elevation" and "prevention of osteoporosis.", Conclusions: No significant differences in most antiemetic effects were found between 1- and 3-day DEX administration. Thus, DEX administration could be shortened from 3 days to 1 day when used in combination with palonosetron., Competing Interests: Declarations. Conflict of interest: Kazuhisa Nakashima received honoraria from Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., and Eli Lilly Japan K.K. Michiyasu Murakami received honoraria from Taiho Pharmaceutical Co., Ltd. Eriko Satomi received honoraria from Shionogi & Co., Ltd. Masayuki Takeda received honoraria from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., and Bayer. Takako Eguchi Nakajima received research funding from KBBM, Inc. and Takeda Pharmaceutical Co., Ltd. Junichi Nishimura received honoraria from Taiho Pharmaceutical Co., Ltd. Narikazu Boku received honoraria from Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Eli Lilly Japan K.K. Koji Matsumoto received honoraria from MSD K.K., Kyowa Kirin Co., Ltd., and Chugai Pharmaceutical Co., Ltd. as well as research funding from Daiichi Sankyo Co., Ltd., MSD K.K., Gilead Sciences, Inc., and Eli Lilly Japan K.K. Nobuyuki Yamamoto received honoraria from MSD K.K., Accuray Japan K.K., AstraZeneca K.K., Abbvie Inc., Amgen Inc., Ono Pharmaceutical Co., Ltd., Guardant Health Japan Corp., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Chugai Foundation for Innovative Drug Discovery Science, Lao Tsumura Co., Ltd., Terumo Corporation, Eli Lilly Japan K.K., Nippon Kayaku Co., Ltd., Novartis AG, Pfzer Global Supply Japan Inc., Merck Biopharma Co., Ltd, Pfzer Global Supply Japan Inc., Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., and USACO Corporation, as well as legal fees in case of lawsuit from Taiho Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan, Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Nippon Kayaku Co., Ltd., Prime Research Institute for Medical RWD, Inc., AstraZeneca K.K., and A2 Healthcare Corporation. Other authors declare that they have no conflict of interest. Ethical approval: Not applicable. Informed consent: Formal consent was not required for this type of study. Consent to participate: Not applicable. Consent for publication: All authors consented to the publication of this study., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Postoperative nausea and vomiting (PONV) are common and distressing complications following neurosurgical procedures, affecting up to 73 % of patients undergoing craniotomy. Therefore, we aimed to assess the placebo-controlled efficacy of 5-HT3 antagonists to prevent PONV following supratentorial craniotomies., Methods: We searched Medline, Web of Science, and Embase databases following PRISMA guidelines for RCTs comparing the outcomes of prophylactic use of 5-HT3 antagonists with placebo to prevent PONV following supratentorial craniotomy. We pooled odds ratios (OR) with 95 % confidence intervals with a random-effects model. I 2 statistics was used to assess heterogeneity., Results: Five RCTs, comprising 347 patients, of which 145 received a placebo, were included. The analysis identified a lower likelihood of early postoperative vomiting in 5-HT3 antagonists group (OR=0.47; 95 % CI: 0.24-0.91, p<0.05; I 2 =7 %), a lower likelihood of vomit within the 24-h period in 5-HT3 antagonists group (OR=0.27; 95 % CI: 0.15-0.48, p<0.01; I 2 =40 %), a lower likelihood of nausea within the 24-h period in 5-HT3 antagonists group (OR=0.47; 95 % CI: 0.28-0.72, p<0.01; I 2 =34 %), and a lower likelihood of rescue interventions in 5-HT3 antagonists group (OR = 0.18; 95 % CI: 0.10-0.34; I 2 = 0 %. Subgroup analyses focusing on ondansetron also identified a lower likelihood of nausea and vomiting within the 24-h period in the 5-HT3 antagonist group., Conclusion: This systematic review and meta-analysis identified that 5-HT3 antagonists are effective in preventing PONV in the postoperative period following supratentorial craniotomy when compared to placebo. Our findings provide synthesized and robust evidence derived from randomized studies to support the use of 5-HT3 antagonists in clinical practice., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Chemotherapy-induced nausea and vomiting (CINV) commonly affects patient quality of life and the overall effectiveness of chemotherapy. This study aimed to evaluate whether adding neurokinin-1 receptor antagonists (NK1RAs) to 5-hydroxytryptamine-3 receptor antagonists (5-HT 3 RAs) and corticosteroids provides clinically meaningful benefits in preventing CINV in patients receiving moderately emetogenic chemotherapy (MEC)., Methods: We conducted a systematic review of PubMed, Cochrane Library, and Ichushi-Web to identify clinical studies evaluating NK1RAs combined with 5-HT 3 RAs and dexamethasone for managing CINV in MEC. The endpoints were complete response (CR), complete control (CC), total control (TC), adverse events, and costs. The data were analyzed using a random effects model., Results: From 142 articles identified, 15 randomized controlled trials (RCTs), involving 4,405 patients, were included in the meta-analysis. Approximately 60% of the patients received carboplatin (CBDCA)-based chemotherapy. The meta-analysis showed that triplet antiemetic prophylaxis with NK1RA was significantly more effective for achieving CR than doublet prophylaxis in each phase. Regarding CC, the triplet antiemetic prophylaxis was significantly more effective than the doublet in the overall (risk difference [RD]: 0.11, 95% confidence interval [CI]: 0.06-0.17) and delayed (RD: 0.08, 95% CI: 0.02-0.13) phases. For TC, no significant differences were observed in any phase. Adding NK1RA did not cause adverse events., Conclusions: Adding NK1RA to CBDCA-based chemotherapy has shown clinical benefits. However, the clinical benefits of NK1RA-containing regimens for overall MEC have not yet been established and require RCTs that exclusively evaluate MEC regimens other than CBDCA-based chemotherapy., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives: To investigate the perception of community pharmacists on the down-scheduling of 5-HT3 antagonists to pharmacist-only-medicine for treatment of acute nausea and/or vomiting in Australia. Methods: A nationwide anonymous survey targeting Australian community pharmacists was conducted from April to May 2023. Responses were collected and analysed quantitively or qualitatively, where appropriate. Key findings: Participants reported that 5-HT3 antagonists were effective at treating nausea and/or vomiting and would likely recommend their use. Training is required to manage supply due to concerns related to their side effects. Conclusion: Participants supported down-scheduling of 5-HT3 antagonists for the treatment of nausea and/or vomiting in Australia. A pilot study on the provision of 5-HT3 antagonists by pharmacists is recommended as is the development of guidelines for pharmacist-only supply before down-scheduling is considered., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The increasing prevalence of alcohol use disorder (AUD) and the parallel surge in alcohol-associated liver disease (ALD) emphasize the urgent need for comprehensive alcohol management strategies. Low-dose ondansetron (AD04, a 5-HT3 antagonist) was shown recently to be a promising treatment for AUD with a specific genotypic profile (5-marker). The liver safety of AD04 has never been evaluated in subjects with AUD. The aim of the present study was to assess the liver safety profile of AD04 compared with placebo in subjects with AUD., Methods: Liver biochemical parameters were assessed in subjects with AUD with a 5-marker genetic profile who participated in a Phase 3 randomized controlled trial and received either twice-daily, low-dose AD04 (ondansetron 0.33 mg twice daily) or matching placebo, combined with brief psychosocial counseling. ALT, AST, GGT, Serum Bilirubin, MCV, and Prothrombin were evaluated at weeks 0, 12, and 24. Adverse cardiac events, general well-being, and study completion were also assessed., Results: Low-dose AD04 did not significantly change biochemical markers of liver injury, such as ALT, AST, and Serum Bilirubin. While patients with AUD displayed elevated GGT levels, typically associated with increased alcohol consumption, this parameter remained unaffected by low-dose AD04. Notably, no significant adverse effects were observed due to oral low-dose AD04 treatment., Conclusions: Low-dose AD04 has the potential to be a safe treatment option for subjects with AUD and ALD, indicating the need for an RCT for this specific cohort. Such a trial would pave the way for the design of a precision treatment for combined AUD with ALD., Competing Interests: Declaration of competing interest All authors are paid consultants of Adial Pharmaceuticals Inc. Bankole Johnson is an officer of Adial Pharmaceuticals Inc., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Variable benefits have been reported from the adjunctive use of simvastatin and the 5HT3 receptor antagonist, ondansetron, in patients with schizophrenia. We investigated their independent efficacy and possible synergy to improve negative symptoms of schizophrenia within a single trial., Methods: A 6-month, randomised, double-blind, placebo-controlled trial with a 4-arm, 2 × 2 factorial design, in three centres in Pakistan. In total, 303 people with stable treated schizophrenia aged 18-65 were randomly allocated to add-on ondansetron, simvastatin, both or neither. The primary outcome was a Positive and Negative Syndrome Scale (PANSS) negative score at 3 and 6 months., Results: Mixed model analysis and analysis of covariance revealed no main effects of simvastatin or ondansetron but a significant negative interaction between them ( p  = 0.03); when given alone, both drugs significantly reduced negative symptoms compared to placebo but they were ineffective in combination. Individual treatment effects versus placebo were -1.9 points (95%CIs -3.23, -0.49; p  = 0.01) for simvastatin and -1.6 points for ondansetron (95%CIs -3.00, -0.14; p  = 0.03). Combined treatment significantly increased depression and side effects. In those with less than the median 5 years of treatment, ondansetron improved all PANSS subscales, global functioning measures and verbal learning and fluency, whereas simvastatin did not., Conclusion: Small improvement in negative symptoms on simvastatin and ondansetron individually are not synergistic in combination in treating negative symptoms of schizophrenia. Ondansetron showed broad efficacy in patients on stable antipsychotic treatment within 5 years of illness. The findings suggest that ondansetron should be evaluated in patients at risk of psychosis or early in treatment., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: I.B.C. and N.H. have given lectures and advice to Eli Lilly, Bristol Myers Squibb, Lundbeck, Astra Zeneca and Janssen pharmaceuticals for which they or their employing institution have been reimbursed. M.I.H. has served as an advisor to MindSet Pharma, Psyched Therapeutics and Wake Network and reports grants from the Brain and Behavior Research Foundation, Canadian Institutes of Health Research, CAMH Foundation, Physician’s Services Incorporated Foundation and University of Toronto. M.I.H., I.B.C. and N.H. were previously trustees of the Pakistan Institute of Learning and Living. B.D. has share options in P1vital.com and is a PI on MRC grant MRC grant MR/S037675/1.

Background: Acetaminophen and 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are administered as standard prophylaxes for postoperative pain, nausea, and vomiting. Preclinical studies, however, suggest that 5-HT3 antagonists may compromise acetaminophen's analgesic effect. This hospital registry study investigates whether 5-HT3 antagonists mitigate the analgesic effect of prophylactic acetaminophen in a perioperative setting., Methods: This study included 55,016 adult patients undergoing general anesthesia for ambulatory procedures at a tertiary healthcare center in Massachusetts from 2015 to 2022. Using binary exposure variables and a comprehensive selection of preplanned patient- and procedure-related covariates for confounder control, the authors investigated whether intraoperative 5-HT3 antagonists affected the association between pre- or intraoperative acetaminophen and postoperative opioid consumption, gauged by opioid dose in milligram oral morphine equivalents (OME) administered in the postanesthesia care unit. A multivariable, zero-inflated negative binomial regression model was applied., Results: A total of 3,166 patients (5.8%) received only acetaminophen, 15,438 (28.1%) only 5-HT3 antagonists, 31,850 (57.9%) both drugs, and 4,562 (8.3%) neither drug. The median postanesthesia care unit opioid dose was 7.5 mg OME (interquartile range, 7.5 to 14.3 mg OME) among 16,640 of 55,016 (30.2%) patients who received opioids, and the mean opioid dose was 3.2 mg OME across all patients (maximum cumulative dose, 20.4 mg OME). Acetaminophen administration was associated with a -5.5% (95% CI, -9.6 to -1.4%; P = 0.009; adjusted absolute difference, -0.19 mg OME; 95% CI, -0.33 to -0.05; P = 0.009) reduction in opioid consumption among patients who did not receive a 5-HT3 antagonist, while there was no effect in patients who received a 5-HT3 antagonist (adjusted absolute difference, 0.00 mg OME; 95% CI, -0.06 to 0.05; P = 0.93; P for interaction = 0.013)., Conclusions: A dose-dependent association of pre- or intraoperative acetaminophen with decreased postoperative opioid consumption was not observed when 5-HT3 antagonists were coadministered, suggesting that physicians might consider reserving 5-HT3 antagonists as rescue medication for postoperative nausea or vomiting when acetaminophen is administered for pain prophylaxis., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Background: Inhibition of 5-HT3 (5-Hydroxyl Tryptamine) receptors is known to enhance morphine analgesia in animal models. We tested the efficacy of azasetron, a 5-HT3 receptor antagonist, on postoperative chronic pain after pulmonary surgery in a randomized triple-blind controlled study., Methods: A total of 250 patients who were scheduled to receive pulmonary surgery were randomized to patient-controlled analgesia (PCA) using 200 µg sufentanil with normal saline or 200 µg sufentanil with 20 mg azasetron. The numerical rating scale of pain (NRS) was recorded at baseline, postoperative day (POD) 1, 2, 3, 90, and 180. Negative binomial regression was used to identify associated factors for postoperative NRS six months after surgery., Results: The results showed that azasetron did not affect the primary outcomes: the incidence of postoperative chronic pain on POD90 and 180. However, azasetron decreased postoperative NRS at rest and activity on POD1, 2, and 3. Furthermore, azasetron decreased postoperative nausea and vomiting on POD1 and 2. Univariate and multivariate negative binomial regression analysis identified preoperative pain, smoking, drinking and open surgery are risk factors of chronic pain six months after surgery., Conclusions: Azasetron did not affect the incidence of chronic pain after pulmonary surgery. The presence of preoperative pain, smoking, drinking, and open surgery were found to be associated with chronic pain six months after surgery., Clinical Trial Registration: The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200060139), 20/05/2022; the site url is https://www.chictr.org.cn/ ., (© 2024. The Author(s).)

Introduction: Selective 5-hydroxytryptamine 3 receptor (5-HT3) antagonists are commonly used to prevent nausea and vomiting (NV) after cesarean section, but the comparative efficacy of different 5-HT3 antagonists remains unclear. This network meta-analysis aimed to determine which 5-HT3 antagonists might be the preferred choice for preventing NV in parturient scheduled for elective cesarean delivery under spinal anesthesia., Evidence Acquisition: PubMed, EMBASE, Cochrane library, and Web of Science were searched for relevant randomized controlled trials (RCTs) published before August 24, 2023. Random network meta-analysis was performed using Stata 14.0 to estimate the efficacy of different 5-HT3 antagonists in preventing intra- and post-operative NV., Evidence Synthesis: Twenty-eight studies involving seven dosing regimens of three 5-HT3 antagonists were included. Pooled results showed that ondansetron 12 mg was superior to other six dosing regimens in the prevention of postoperative NV (PONV), PON, and POV, with the ranking probability of 80.2%, 95.8%, and 87.7%, respectively, followed by granisetron two mg. Ondansetron 4 mg might be the first choice for preventing intraoperative NV (IONV) (92.8%), with the least use of postoperative rescue antiemetics (90.6%). Granisetron 3 mg and tropisetron 2 mg might be the best options for preventing ION and IOV, respectively., Conclusions: Based on available data, ondansetron 12 mg may have the best efficacy in preventing PONV, PON, and POV. Additionally, more studies are warranted to compare the safety of ondansetron 12 mg versus granisetron two mg.

Background: Dopamine antagonists, 5-HT 3 antagonists, and dexamethasone are frequently used in obstetrics to prevent postoperative nausea and vomiting (PONV). However, the superiority of any drug class is yet to be established. This network meta-analysis aimed to compare the efficacy of these antiemetics for PONV prophylaxis in women receiving neuraxial morphine for Caesarean delivery., Methods: We searched PubMed, Embase, CENTRAL, Web of Science, and Wanfang Data for eligible randomised controlled trials. Primary outcomes were the incidences of postoperative nausea (PON) and postoperative vomiting (POV) within 24 h after surgery. We used a Bayesian random-effects model and calculated odds ratios with 95% credible intervals for dichotomous data. We performed sensitivity and subgroup analyses for primary outcomes., Results: A total of 33 studies with 4238 women were included. In the primary analyses of all women, 5-HT 3 antagonists, dopamine antagonists, dexamethasone, and 5-HT 3 antagonists plus dexamethasone significantly reduced PON and POV compared with placebo, and 5-HT 3 antagonists plus dexamethasone were more effective than monotherapy. In the subgroup analyses, similar results were seen in women receiving epidural morphine or intrathecal morphine alone but not in women receiving intrathecal morphine with fentanyl or sufentanil. However, most included studies had some concerns or a high risk of bias, and the overall certainty of the evidence was low or very low., Conclusions: Combined 5-HT 3 antagonists plus dexamethasone are more effective than monotherapy in preventing PONV associated with neuraxial morphine after Caesarean delivery. Future studies are needed to determine the role of prophylactic antiemetics in women receiving intrathecal morphine and lipophilic opioids., Systematic Review Protocol: PROSPERO CRD42023454602., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Introduction: There has been a lack of research comparing the efficacy of various treatments for low anterior resection syndrome (LARS)., Methods: We conducted a comprehensive search across six electronic databases and a paired meta-analysis was undertaken to assess the effectiveness of the interventions. Furthermore, a network meta-analysis was utilized to compare the efficacy of different treatments for LARS., Results: This study encompassed nine randomized controlled trials, involving a total of 450 patients. Compared to routine care, 5-HT3 receptor antagonists (follow-up<3 months) and percutaneous tibial nerve stimulation (3 months ≤ follow-up <6 months) were effective in reducing the LARS score. Pelvic floor rehabilitation (follow-up≤3 months) was effective in decreasing daily number of bowel movements when compared to routine care. The network meta-analysis indicated that 5-HT3 receptor antagonists (follow-up<3 months) were the most effective in reducing both the LARS score and the daily number of bowel movements. Transanal irrigation (3 months ≤ follow-up ≤ 12 months) was most effective in reducing the LARS score. Additionally, 5-HT3 receptor antagonists demonstrated relative efficacy in improving patients' quality of life (follow-up ≤ 1 month)., Conclusions: This review indicates that 5-HT3 receptor antagonists and anal irrigation show significant promise in the treatment of LARS. Nevertheless, the contributions of percutaneous tibial nerve stimulation and pelvic floor rehabilitation to LARS treatment should not be overlooked. Given the clinical heterogeneity observed among the studies, the results should be interpreted with caution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Elsevier Ltd, BASO ∼ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: To investigate the association between adherence to guideline-recommended risk-based postoperative nausea and vomiting (PONV) prophylaxis, the antiemetics used for PONV prophylaxis, and the incidence of PONV in patients who were underwent general anesthesia before and after 5-HT3 receptor antagonists became available., Methods: Patients (≥ 20 years old) who were extubated after scheduled surgery and returned to general wards between January 2021 and February 2022 and between June 2022 and July 2023 were included. Risk factors included age < 50, female, motion sickness, nonsmoker, surgical factors, and postoperative opioid use. Two and three or more prophylaxis were recommended for patients with one or two and three or more risk factors, respectively. The primary outcome was the number of patients who received adequate prophylaxis, and the secondary outcomes were antiemetic agents used during anesthesia and the incidence of PONV on postoperative days 0 and 1. PONV was defined as documented PONV or rescue antiemetic administration., Results: From January 2021 to February 2022 and from June 2022 to July 2023, 2342 and 2682 patients were included, respectively. Before ondansetron became available, more D2 receptor antagonists were used (p < 0.001), and after ondansetron became available, both ondansetron (p < 0.001) and propofol (p < 0.001) were given more frequently. Before and after ondansetron became available, the number of patients with adequate prophylaxis was 3.7% and 9.2%, respectively (p < 0.001), and the incidence of PONV on postoperative days 0 and 1 was 44.6% and 44.0%, respectively (p = 0.67)., Conclusion: The availability of ondansetron increased the number of patients with adequate PONV prophylaxis, but did not decrease the incidence of PONV., (© 2024. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Radiotherapy combined with temozolomide (TMZ+RT) is the primary treatment for high-grade glioma. TMZ is classified as a moderate emetic risk agent and, thus, supportive care for nausea and vomiting is important. In Nagoya University Hospital, all patients are treated with a 5-hydroxy-tryptamine 3 receptor antagonist (5-HT 3 RA) for the first 3 days. The daily administration of 5-HT 3 RA is resumed after the 4th day based on the condition of patients during TMZ+RT. Therefore, the present study investigated risk factors for nausea and vomiting in patients requiring the daily administration of 5-HT 3 RA. Patients with high-grade glioma who received TMZ+RT between January 2014 and December 2019 at our hospital were included. Patients were divided into two groups: a control group (patients who did not resume 5-HT 3 RA) and resuming 5-HT 3 RA group (patients who resumed 5-HT 3 RA after the 4th day), and both groups were compared to identify risk factors for nausea and vomiting during TMZ+RT. There were 78 patients in the control group (68%) and 36 in the resuming 5-HT 3 RA group (32%). A multivariate analysis of patient backgrounds in the two groups identified age <18 years, PS 2 or more, and occipital lobe tumors as risk factors for nausea and vomiting. Nausea and vomiting were attenuated in 30 patients (83%) in the resuming 5-HT 3 RA group following the resumption of 5-HT 3 RA. The results obtained highlight the importance of extracting patients with these risk factors before the initiation of therapy and the early resumption or daily administration of 5-HT 3 RA according to the condition of each patient., Competing Interests: The authors declare no conflict of interest.

Purpose: Chemotherapy-induced nausea and vomiting (CINV) are common adverse events in patients undergoing emetogenic chemotherapy. Palonosetron, a second-generation 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA), has demonstrated non-inferiority to first-generation 5-HT3 RAs for CINV in pediatric patients. Although palonosetron has a long half-life and prolonged antiemetic action, its efficacy against delayed CINV in pediatric patients is not well understood. Therefore, this meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy of palonosetron for delayed CINV in pediatric patients., Methods: A literature search of MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science databases was performed. A meta-analysis was performed using forest plots, and risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. A funnel plot was constructed to explore publication bias., Results: The literature search retrieved 842 records, of which 23 full-text articles were assessed, including six RCTs. Meta-analysis of four RCTs that reported on the complete response (CR: defined as no emesis and no rescue medication) rate for delayed CINV revealed that palonosetron was statistically superior to first-generation 5-HT3 RAs (RR = 1.21 [95% CI 1.09-1.35]; p < 0.01). Although the number of studies included was small, no publication bias was observed in the funnel plots. In addition, the CR rate for overall and acute CINV was also significantly higher for palonosetron (RR = 1.25 [95% CI 1.01-1.54]; p = 0.04 and RR = 1.06 [95% CI 1.01-1.12]; p = 0.03, respectively)., Conclusion: Palonosetron is effective in the prophylaxis of delayed CINV in pediatric patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Nausea is a common and unpleasant sensation for which current therapies such as serotonin (5-HT 3 ) antagonists are often ineffective, while also conferring a risk of potential adverse events. Isopropyl alcohol (IPA) has been proposed as a treatment for nausea. We aimed to compare IPA with 5-HT 3 antagonists for the treatment of nausea across all clinical settings., Methods: MEDLINE, EMBASE, PubMed, CENTRAL and CINAHL were searched from inception to 17 July 2023 for randomised controlled trials (RCTs) comparing inhaled IPA and a 5-HT 3 antagonist for treatment of nausea. Severity and duration of nausea, rescue antiemetic use, adverse events and patient satisfaction were the outcomes sought. Risk of bias (RoB) was assessed using Cochrane RoB 2. Random-effects model was used for meta-analysis. Combination of meta-analyses and narrative review was used to synthesise findings. The evidence was appraised using GRADE., Results: From 1242 records, 4 RCTs were included with 382 participants. Participants receiving IPA had a significantly lower mean time to 50% reduction in nausea (MD - 20.06; 95% CI - 26.26, - 13.85). Nausea score reduction at 30 min was significantly greater in the IPA group (MD 21.47; 95% CI 15.47, 27.47). IPA led to significantly reduced requirement for rescue antiemetics (OR 0.60; 95% CI 0.37, 0.95; p = 0.03). IPA led to no significant difference in patient satisfaction when compared with a 5-HT 3 antagonist. The overall GRADE assessment of evidence quality ranged from very low to low., Conclusion: IPA may provide rapid, effective relief of nausea when compared with 5-HT 3 antagonists., (© 2023. The Author(s).)

Pain in Parkinson's disease (PD) is increasingly recognized as a major factor associated with poor life quality of PD patients. However, classic therapeutic drugs supplying dopamine have limited therapeutic effects on PD-related pain. This suggests that there is a mechanism outside the dopamine system that causes pain in PD. Our previous study demonstrated that 6-OHDA induced PD model manifested hyperalgesia to thermal and mechanical stimuli and decreased serotonin (5-hydroxytryptamine; 5-HT) in the spinal dorsal horn (SDH). Several 5-HT receptor subtypes have been confirmed to be associated with nociception in the spinal cord, such as 5-HT1A receptor, 5-HT1B receptor, 5-HT2 receptor, 5-HT3 receptor, and 5-HT7 receptor. Most research has shown that 5-HT1A receptor and 5-HT3 receptor play a key role in pain transmission in the spinal cord. We hypothesized that hyperalgesia of 6-OHDA rats may be related to increased excitability of SDH neurons, and functional change of 5-HT3 receptor may reverse the hyperalgesia of 6-OHDA lesioned rats and decrease cell excitability of SDH neurons. To test this hypothesis, we used whole-cell patch-clamp and pharmacological methods to evaluate the effect of 5-HT3 receptor and 5-HT1A receptor on the hyperalgesia of 6-OHDA rats. The results suggested that increased excitability in SDH neurons could be reversed by 5-HT3 receptor antagonist ondansetron (20 μmol/L) and palosetron (10 μmol/L), but not 5-HT3 receptor agonist m-CPBG (30 μmol/L) and SR 57,727 (10 μmol/L), 5-HT1A receptor agonist 8-OH DPAT (10 μmol/L) and eptapirone (10 μmol/L) and 5-HT1A receptor antagonist WAY-100635 (10 μmol/L) and p-MPPI (10 μmol/L). Intrathecal injection of ondansetron (0.1 mg/kg) but not m-CPBG (0.1 mg/kg), 8-OH DPAT (0.1 mg/kg), and WAY-100635 (0.1 mg/kg) significantly attenuated the mechanical hyperalgesia and thermal hyperalgesia in 6-OHDA lesioned rats. In conclusion, the present study suggests that inhibition of spinal 5-HT3 receptor and SDH neuronal excitability alleviates hyperalgesia in PD rats. Our study provides a novel mechanism or therapeutic strategy for pain in patients with PD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Olanzapine has been reported to be an effective antiemetic in patients receiving carboplatin-based chemotherapy. However, the efficacy of a neurokinin-1 receptor antagonist (NK 1 RA) added to olanzapine, a 5-hydroxytryptamine-3 receptor antagonist (5-HT 3 RA), and dexamethasone (DEX) has not been proven. This study aimed to assess the efficacy and safety of NK 1 RA, in combination with three-drug antiemetic regimens containing olanzapine, in preventing nausea and vomiting induced by carboplatin-based chemotherapy., Methods: Data were pooled for 140 patients receiving carboplatin-based chemotherapy from three multicenter, prospective, single-arm, open-label phase II studies that evaluated the efficacy and safety of olanzapine for chemotherapy-induced nausea and vomiting. The propensity score of the co-administration of NK 1 RA was estimated for each patient using a logistic regression model that included age, sex, and carboplatin dose. We analyzed a total of 62 patients, who were treated without NK 1 RA (non-NK 1 RA group: 31 patients) and with NK 1 RA (NK 1 RA group: 31 patients). The patients were selected using propensity score matching., Results: The complete response rate (without emetic episodes or with no administration of rescue medication) in the overall period (0-120 h post carboplatin administration) was 93.5% in the non-NK 1 RA group and 96.8% in the NK 1 RA group, with a difference of -3.2% (95% confidence interval, -18.7% to 10.9%; P = 1.000). In terms of safety, there was no significant difference between the groups in daytime sleepiness and concentration impairment, which are the most worrisome adverse events induced by olanzapine., Conclusions: The findings suggest that antiemetic regimens consisting of olanzapine, 5HT 3 RA, and DEX without NK 1 RA may be a treatment option for patients receiving carboplatin-based chemotherapy., (© 2022. The Author(s).)

Introduction: Triple antiemetic therapy with neurokinin-1 receptor antagonist, 5-hydroxytryptamine type 3 receptor antagonist, and dexamethasone has been widely recommended for high emetogenic chemotherapeutic (HEC) agents and regimens, including anthracycline combined with cyclophosphamide (AC). The addition of olanzapine (OLZ) 5 mg or 10 mg to the recommended triple antiemetic therapy has demonstrated superiority in antiemetic efficacy compared with the standard triplet therapy for a cisplatin-based HEC regimen. Although OLZ plus the triple antiemetic treatment may also be effective for patients on an AC-based HEC regimen, no study has investigated its efficacy at a lower dose of 5 mg., Methods and Analysis: To assess whether 5 mg OLZ, as compared with placebo, in combination with triple combination therapy, significantly improves nausea and vomiting, we are conducting a randomised, parallel-group controlled clinical trial with a total of 500 patients at 15 study centres in Japan. The primary outcome is the complete response rate, defined as no emetic episodes and no use of rescue medication during 120 hours after the initiation of chemotherapy. Treatment group comparison for the primary endpoint will be done by using the Cochran-Mantel-Haenszel test., Ethics and Dissemination: The study was approved by the institutional review board of Juntendo University Hospital and relevant approval was obtained from all participating centres. All participants will be required to provide written informed consent. The trial results will be reported at conferences and in peer-reviewed journals., Trial Registration Number: Japan Registry of Clinical Trials (jRCT) jRCT1031200134; protocol date: 30 July 2020, version: 1.3, approval: 25 August 2020., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Chemotherapy-induced nausea and vomiting (CINV) commonly occurs after chemotherapy, adversely affecting patients' quality of life. Recently, studies have shown inconsistent antiemetic effects of two common 5-hydroxytryptamine 3 receptor antagonists, namely, palonosetron and granisetron. Therefore, we conducted a meta-analysis to evaluate the effectiveness of palonosetron versus granisetron in preventing CINV., Methods: Relevant studies were obtained from PubMed, Embase, and Cochrane databases. The primary outcome was the complete response (CR) rate. Secondary outcomes were headache and constipation events., Results: In total, 12 randomized controlled trials and five retrospective studies were reviewed. Palonosetron was consistently statistically superior to granisetron in all phases in terms of the CR rate (acute phases: odds ratio [OR] = 1.28, 95% confidence interval [CI] = 1.06-1.54; delayed phases: OR = 1.38, 95% CI = 1.13-1.69; and overall phases: OR = 1.37, 95% CI = 1.17-1.60). Moreover, a non-significant difference was found between the two groups in terms of the headache event, but the occurrence of the constipation event was lower in the granisetron group than in the palonosetron group., Conclusion: Palonosetron showed a higher protective efficacy in all phases of CINV prevention, especially in delayed phases, and no relatively severe adverse effects were observed., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Complex regional pain syndrome (CRPS) is caused by injuries from fracture after trauma and orthopaedic surgical procedures in the hind limbs. The symptoms of CRPS include warmth, pain, allodynia, and hyperalgesia. It is known that 5-hydroxytryptamine 3 (5-HT3) receptors contribute to hyperalgesia, but their role has not yet been fully elucidated. This study investigated the mechanism of pain relief when a 5-HT3 receptor antagonist was administered in a CRPS animal model., Materials and Methods: To establish a CRPS animal model, 10-week-old Sprague-Dawley rats were used in the experiment. On the fourth week post tibial fracture surgery, we performed the von Frey test to measure mechanical allodynia. After performing behavioural tests, we collected blood and tissue samples after sacrificing the animals. Enzyme-linked immunosorbent assay and western blot were also performed., Results: The experimental tibia fracture model-induced CRPS animals elicited increased 5-HT3 receptor expression, and the 5-HT transporter was decreased in the brain stem after 4 weeks of surgical intervention. Additionally, in CRPS-induced animals, both the concentration of substance P and the level of interleukin 6 were increased peripherally and centrally. Treatment with the 5-HT3 receptor antagonist, ramosetron, exerted an analgesic effect in the paw withdrawal test and was dependent on the attenuation of the 5-HT3 receptor population with inflammatory pain mediators., Conclusions: These data suggest that treatment with the 5-HT3 receptor antagonist, ramosetron, in experimental CRPS animal models alleviated pain-related behaviours and may be a new therapeutic option or potential therapeutic agent for patients with CRPS.

Purpose: Proper monitoring and management of chemotherapy-induced nausea and vomiting (CINV) with antiemetics is crucial for cancer patients. This study aimed to evaluate the use of antiemetics for the treatment of highly emetogenic chemotherapy (HEC) including carboplatin in the real-world setting in Spain., Methods: A representative panel of cancer specialists was asked to collect information about the antiemetic treatments provided to patients receiving chemotherapy. Records formed part of the Global Oncology Monitor © database (Ipsos Healthcare, London, UK). Chemotherapy data were extrapolated using Ipsos Healthcare's projection methodology., Results: A total of 73 experts were finally included. Data from 9519 patients, estimated to be representative of 202,084 patients, were collected. HEC (and carboplatin-based chemotherapy) was administered to 73,118 (36%) patients, cisplatin-based therapy being the most frequent treatment (n = 34,649, 47.38%). Neurokinin-1 receptor antagonists (NK 1 RAs) alone or in combination were used as prophylaxis for CINV in 14,762 (20%) patients, while the combination of NK 1 RA with 5-hydroxytryptamine-3 receptor antagonist (5-HT 3 RAs) and dexamethasone as recommended by the international guidelines was used in 5849 (8%) patients only. No antiemetic prophylaxis was administered to 8.46% of the patients receiving HEC (n = 6189). Physicians classified cisplatin-, anthracycline-cyclophosphamide (AC-), and carboplatin-based regimens as HEC in 63%, 22% and 4% of the cases, respectively., Conclusions: The use of NK 1 RA-containing regimens for CINV prevention in patients treated with HEC was less than expected, suggesting poor adherence to international antiemetic guidelines., (© 2021. The Author(s).)

In line with recent clinical trials demonstrating that ondansetron, a 5-HT 3 receptor (5-HT 3 R) antagonist, ameliorates cognitive deficits of schizophrenia and the known procognitive effects of 5-HT 6 receptor (5-HT 6 R) antagonists, we applied the hybridization strategy to design dual-acting 5-HT 3 /5-HT 6 R antagonists. We identified the first-in-class compound FPPQ , which behaves as a 5-HT 3 R antagonist and a neutral antagonist 5-HT 6 R of the Gs pathway. FPPQ shows selectivity over 87 targets and decent brain penetration. Likewise, FPPQ inhibits phencyclidine (PCP)-induced hyperactivity and displays procognitive properties in the novel object recognition task. In contrast to FPPQ , neither 5-HT 6 R inverse agonist SB399885 nor neutral 5-HT 6 R antagonist CPPQ reversed (PCP)-induced hyperactivity. Thus, combination of 5-HT 3 R antagonism and 5-HT 6 R antagonism, exemplified by FPPQ , contributes to alleviating the positive-like symptoms. Present findings reveal critical structural features useful in a rational polypharmacological approach to target 5-HT 3 /5-HT 6 receptors and encourage further studies on dual-acting 5-HT 3 /5-HT 6 R antagonists for the treatment of psychiatric disorders.

Schisandrin C (Sch C) is one of the main components of Schisandra chinensis (Schisandra). Since the olden times, Schisandra has been used as a traditional herbal medicine in Asia. Recent studies have shown that Schisandra is effective against irritable bowel syndrome (IBS) in an animal model and affects IBS through the 5-HT 3A pathway in the IBS rat model. However, there lacks fundamental research on the interaction of specific components of Schisandra with the 5-HT 3A receptor for the treatment of IBS. We hypothesized that a component of Schisandra binds to the 5-HT 3A receptor and identified Sch C via a screening work using two electrode-voltage clamps (TEVC). Thus, we aimed to elucidate the neuropharmacological actions between Sch C and the 5-HT 3A receptor at molecular and cellular levels. Co-treatment of Sch C with 5-HT inhibited I 5-HT in a reversible, concentrate-dependent, like-competition, and voltage-independent manner, and IC 50 values of Sch C. Besides, the main binding positions of Sch C were identified through 3D modeling and point mutation were V225A and V288Y on 5-HT 3A receptor. Thus, we suggest the potential of Sch C in treating IBS in a manner that suppresses excessive neuronal serotonin signaling in the synapse of sensory neurons and enterochromaffin (EC) cells. In conclusion, the results demonstrate the mechanism of interaction between Sch C and 5-HT 3A receptor and reveal Sch C as a novel antagonist., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: No effective treatment exists for anterior resection syndrome (ARS) following sphincter-saving surgery for rectal cancer. This RCT assessed the safety and efficacy of a 5-HT3 receptor antagonist, ramosetron, for ARS., Methods: A single-centre, randomized, controlled, open-label, parallel group trial was conducted. Male patients with ARS 1 month after rectal cancer surgery or ileostomy reversal were enrolled and randomly assigned (1 : 1) to 5 μg of ramosetron (Irribow®) daily or conservative treatment for 4 weeks. Low ARS (LARS) score was calculated after randomization and 4 weeks after treatment. The study was designed as a superiority test with a primary endpoint of the proportion of patients with major LARS between the groups. Primary outcome analysis was based on the modified intention-to-treat population. Safety was assessed by monitoring adverse events during the study., Results: : A total of 100 patients were randomized to the ramosetron (49 patients) or conservative treatment group (51 patients). Two patients were excluded, and 48 and 50 patients were analysed in the ramosetron and control groups, respectively. The proportion of major LARS after 4 weeks was 58 per cent (28 of 48 patients) in the ramosetron group versus 82 per cent (41 of 50 patients) in the control group, with a difference of 23.7 per cent (95 per cent c.i. 5.58 to 39.98, P = 0.011). There were minor adverse events in five patients, which were hard stool, frequent stool or anal pain. These were not different between the two groups. There were no serious adverse events., Conclusion: : Ramosetron could be safe and feasible for male patients with ARS., Trial Registration Number: NCT02869984 (http://www.clinicaltrials.gov)., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Type A trichothecene neosolaniol (NEO) is considered a potential risk to human and animal health by the European Food Safety Authority (EFSA). To date, available data do not allow making conclusions about the toxicological properties of this toxin. Trichothecenes have been previously demonstrated to induce emetic responses in mink, and this response has been associated with neurotransmitter peptide YY (PYY) and serotonin (5-hydroxytryptamine, 5-HT). The goal of this study was to compare emetic effects of NEO administered by intraperitoneal and oral routes and relate these effects to PYY and 5-HT. The effective doses resulting in emetic events in 50% of the animals following intraperitoneal and oral exposure to NEO were 0.4 and 0.09 mg/kg bw, respectively. This emetic response corresponded to elevated PYY and 5-HT levels. Blocking the neuropeptide Y2 receptor diminished emesis induction by PYY and NEO. The 5-HT3 receptor inhibitor granisetron completely restrained the induction of emesis by 5-HT and NEO. To summarize, our findings demonstrate that PYY and 5-HT play important roles in the NEO-induced emetic response., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Memantine is used in Alzheimer's disease treatment as a non-competitive modern-affinity strong voltage-dependent N-methyl-D-aspartate receptor antagonist. The fundamental role of these receptors is to bind glutamate: the main excitatory neurotransmitter in the brain, believed to play a crucial role in neuronal plasticity and learning mechanisms. Glutamate transmission plays an important role in all internal CNS structures and maintains the physiological state of the brain. Excessive glutamate transmission can lead to enlarged calcium ion current which may cause neurotoxicity; however, insufficient transmission can drastically alter the information flow in neurons and the brain, potentially causing schizophrenia-like symptoms by replacing lost information with completely new stimuli. Hence, it is possible that the modulation of NMDA activity may give rise to pathophysiological states. Available literature and clinical trials indicate that memantine is well tolerated by patients, with very few and light side effects. There is a belief that memantine may also benefit other conditions such as schizophrenia and depression.

Delayed chemotherapy-induced nausea and vomiting (CINV) is not well controlled in colorectal cancer (CRC) patients undergoing oxaliplatin (L-OHP)-based chemotherapy. Whether neurokinin-1 receptor antagonist addition to a first-generation 5HT 3 antagonist (1st 5-HT 3 RA) and dexamethasone (DEX) is beneficial to these patients remains controversial. Furthermore, whether palonosetron (PALO) or aprepitant (APR) is more effective in controlling delayed CINV is unclear. We, therefore, investigated whether PALO+DEX or 1st 5-HT 3 RA+DEX+APR was more effective in controlling delayed CINV, and the risk factors for delayed CINV, in CRC patients undergoing L-OHP-based chemotherapy. Data were pooled from two prospective observational Japanese studies and a phase III trial to compare CINV incidence between the PALO + DEX (PALO) and 5-HT 3 RA+DEX+APR (APR) groups by propensity score-matched analysis. CINV risk factors were identified using logistic regression models. The CINV incidence was higher in the PALO group than in the APR group. Logistic regression analysis revealed alcohol consumption, motion sickness, and the PALO+DEX regimen as independent risk factors for delayed nausea, and female sex and the PALO+DEX regimen as those for delayed vomiting. Compared with prophylactic PALO + DEX, 1st 5-HT 3 RA+DEX+APR was more effective in controlling delayed CINV. Thus, CRC patients receiving L-OHP-based chemotherapy should be treated with three antiemetics, including APR., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The significant physical and emotional effects of chemotherapy-induced nausea and vomiting (CINV) are experienced by cancer patients. Severe symptoms decrease the patient's quality of life and potentially deters further treatment. The five main forms of CINV (i.e., acute, delayed, anticipatory, breakthrough, and refractory) require different treatment regimens, which often include 5-HT3 receptor antagonists, NK1 receptor antagonists, and corticosteroids. Despite a significant amount of research and development of antiemetic agents, management of CINV remains a great challenge with many needs waiting to be adequately addressed, such as controlling non-acute CINV, developing appropriate CINV treatment protocols for multiple-day chemotherapy patients, and providing options for those prone to CINV despite treatment. Further research is required to optimize CINV management for these patients., (Copyright © 2020. Published by Elsevier Ltd.)

In Parkinson's disease (PD), management of L-3,4-dihydroxyphenylalanine (l-DOPA)-related complications, such as l-DOPA induced dyskinesia and psychosis, remains inadequate, which poses a significant burden on the quality of life of patients. We have shown, in the hemi-parkinsonian rat model of PD, that the selective serotonin type 3 (5-HT 3 ) receptor antagonists ondansetron and granisetron decreased the severity of established dyskinesia, and ondansetron even attenuated the development of dyskinesia. Here, we seek to confirm these favourable data on dyskinesia and to explore the effect of ondansetron on the severity of psychosis-like behaviours (PLBs) in the gold standard model of PD, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned non-human primate. We first determined the pharmacokinetic profile of ondansetron in the marmoset. Subsequently, six MPTP-lesioned marmosets were administered l-DOPA chronically until they exhibited stable and reproducible dyskinesia and PLBs upon each administration of l-DOPA. On behavioural assessment days, ondansetron (0.01, 0.1 and 1 mg/kg) or vehicle was administered in conjunction with l-DOPA, and the severity of dyskinesia, PLBs and parkinsonism was evaluated. Ondansetron 0.1 mg/kg alleviated global dyskinesia severity by 73% (P < 0.0001) and decreased duration of on-time with disabling dyskinesia by 88% (P = 0.0491). Ondansetron 0.1 mg/kg reduced the severity of global PLBs by 80% (P < 0.0001) and suppressed on-time with disabling PLBs (P = 0.0213). Ondansetron enhanced the anti-parkinsonian action of l-DOPA, reducing global parkinsonism by 53% compared to l-DOPA (P = 0.0004). These results suggest that selective blockade of the 5-HT 3 receptor with ondansetron may be an effective approach to alleviate l-DOPA-related complications., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Depression or Major depressive disorder (MDD) is a prolonged condition of sadness. MDD is the most common mental disorder that affects more than 264 million people worldwide. According to the monoamine hypothesis, serotonin (5-hydroxy tryptamine, 5-HT), dopamine (DA) and norepinephrine (NE) are the major neurotransmitters (NTs) involved in depression., Methods: The methodology adopted for writing this review article is essentially based on the secondary literature search through a systematic literature review. This review mainly focussed on the role of 5-HT 3 receptor antagonists (5-HT 3 RA) in depression and comorbid disorders like anxiety., Results: Out of three major NTs mentioned above, serotonin has a predominant role in the pathophysiology of depression. The serotonin type-3 receptors (5-HT 3 R) are well renowned to be expressed in the central nervous system (CNS) in regions which have significance in the vomiting reflex, perception of pain, the reward system, cognition, depression and anxiety control. 5-HT 3 R are the receptors of serotonergic family that belong to ligand-gated ion channel. 5-HT 3 RA inhibit the binding of serotonin to postsynaptic 5-HT 3 R and increases its availability to other receptors like 5- HT 1A , 1B and 1D as well as 5-HT 2 receptors and produces anti-depressant-like effect. 5-HT 3 RA also have an important role in mood and stress disorders. Some of the studies have shown the effectiveness of these agents in stress disorder., Conclusion: The present article focussed on the role of 5-HT 3 R and their antagonists in the treatment of depression and anxiety. Further studies are warranted to prove their efficacy with respect to other standard anti-depressants., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Post dural puncture headache (PDPH) is a common complication in patients following diagnostic or therapeutic lumbar puncture, procedures requiring epidural access, and spinal surgery. Epidural blood patch (EBP), the gold standard for the treatment of this pathology requires training not provided to emergency physicians. In addition, the presence of concomitant pathology and abnormal laboratory values are contraindications to perform EBP. In presence of these limitations, we sought for a non-interventional management of PDPH utilizing high-flow oxygen and pro-serotonin agents. We reviewed the mechanism of action of this therapy METHODS: To illustrate our proposal, we report a series of twelve consecutive patients with PDPH treated with high-flow oxygen therapy at 12 L/min via a non-rebreathing mask and intravenous metoclopramide., Results: All patients were treated with this conservative therapy, no adverse reactions were observed. After the intervention, the headache resolved without further indications for PDPH., Conclusion: Our series suggests that combining high-flow oxygen and pro-serotonin agents such metoclopramide in the ED might be a feasible option as effective as the invasive methods used in treating PDPH. This therapy appears to be efficient and to minimize risk, cost and side effects. It presents an easily accessible alternative that should be considered when PDPH is not a viable option., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Tropisetron and Granisetorn are 5-HT3 antagonists with antiemetic effects. Tropisetron also has a partial agonistic effect on alpha-7 nicotinic acetylcholine receptors (α7 nAChRs). On the other hand, chronic cerebral hypoperfusion (CCH) attenuates cerebral blood flow and impairs cognitive functions. The goal of this study was to investigate the effect of Tropisetron and Granisetron on CCH-induced spatial memory impairment in rats. Forty-eight male Wistar rats were used in this study. 2-VO surgery was done to induce CCH and Radial Eight Arm Maz apparatus was used to evaluate spatial memory (working and reference memory). Tropisetron was injected intraperitoneally at the doses of 1 and 5 mg/kg, and Granisetron was injected intraperitoneally at the dose of 3 mg/kg. Dorsal hippocampal (CA1) neurons count, Interleukin 6 (IL-6) serum level, and serotonin-reuptake transporter (SERT) gene expression were also evaluated. The results showed, CCH impaired working and reference memory, increased IL-6 serum level, and decreased CA1 neurons and SERT expression. Tropisetron at the dose of 5 mg/kg restored all the effects of CCH. However, Granisetron did not restore CCH-induced memory impairment. Furthermore, Granisetron had no effect on IL-6. While, it increased SERT expression and CA1 neurons. In conclusion, Tropisetron but not Granisetron, ameliorated spatial memory impairment induced by CCH. We suggested conducting more detailed studies investigating the role of serotonergic system (5-HT3 receptors and serotonin transporters) and also α7 nAChRs in the effects of Tropisetron.

Background: Of patients receiving moderate emetic risk chemotherapy (MEC), 30-90% experience chemotherapy-induced nausea and vomiting (CINV); however, the optimal antiemetic treatment remains controversial., Methods: In this multicenter, prospective, observational study of adults treated with MEC while receiving chemotherapy for various cancer types in Japan, the enrolled patients kept diaries documenting CINV. All participants received a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone., Results: Of the 400 patients enrolled from May 2013 to January 2015, 386 were eligible for evaluation. The median age was 64 (range, 26-84). The overall complete response (CR; no emetic events and no antiemetic measures) rate was 64%. The proportion of patients showing CR was low in the carboplatin (CBDCA)- and oxaliplatin-based chemotherapy groups, especially among women. We showed that the CR rates in men were high in the CBDCA (AUC5) + etoposide (ETP) (80%), capecitabine plus oxaliplatin (CAPOX) (78%), and CBDCA+ paclitaxel (PTX) groups for lung cancer (73%). Total control (TC; no emetic events, no antiemetic measures, and no nausea) and complete control (CC; no emetic events, no antiemetic measures, and less than mild nausea) were achieved in 51 and 61% of patients, respectively. Logistic regression analysis revealed history of motion sickness, history of pregnancy-associated vomiting and CBDCA-based chemotherapy as risk factors for CR and history of motion sickness and history of pregnancy-associated vomiting as risk factors for TC. Additional, Ages ≥65 years is an independent predictive factor for achieving TC., Conclusions: Our data showed that two antiemetics were insufficient to control CINV in patients receiving CBDCA- or oxaliplatin-based chemotherapy. However, two antiemetics may be sufficiently effective for elderly male patients receiving CBDCA (AUC5) + ETP, CBDCA+PTX for lung cancer, or CAPOX. Additionally, we consider that three antiemetics are necessary for women with colorectal cancer receiving CAPOX. Risk factor analysis related to CR showed that CINV prophylaxis in patients treated with CBDCA-based chemotherapy was generally supportive of the guideline-recommended three antiemetics. However, the control of nausea in patients receiving non-CBDCA-based chemotherapy is a key point to note. The further individualization of antiemetic regimens for patients receiving MEC based on both types of chemotherapy regimens and sex is needed.

Importance: Postoperative delirium is a frequent disorder for patients undergoing surgery and is associated with poor outcomes. Delirium may occur in the immediate period after anesthesia administration and surgery. Tropisetron, which is frequently administrated for postoperative nausea and vomiting, is also a partial agonist of α7 nicotinic acetylcholine receptors associated with neuroprotective effects. Tropisetron may be the potential pharmacological treatment to decrease delirium after noncardiac surgery., Objective: To perform a randomized clinical trial to determine the efficacy and safety of tropisetron for prevention of emergence delirium in patients undergoing noncardiac surgery., Design, Setting, and Participants: This single-center, 2-arm randomized, double-blind, placebo-controlled trial will include 1508 patients undergoing noncardiac surgery. The intervention group will receive 5 mg of intravenous tropisetron before anesthesia induction, and patients in the control group will receive a placebo. The primary end point is the incidence of emergence delirium within 1 hour after tracheal tube removal, measured by the Confusion Assessment Method for the Intensive Care Unit score. The main secondary outcome is the incidence of postoperative delirium measured at 3 days of follow-up. An intention-to-treat principle will be used for all analyses., Discussion: Delirium remains the most common neuropsychiatric complication for patients after surgery. This will be the first randomized clinical study to evaluate whether tropisetron is effective in preventing emergence delirium. Results from this study will provide evidence for alteration of daily practice., Trial Registration: ClinicalTrials.gov Identifier: NCT04027751.

Post-transplantation cyclophosphamide (PTCy) is a new method to prevent graft-versus-host disease after allogeneic hematopoietic cell transplantation. Although the use of dexamethasone is recommended as prophylaxis against chemotherapy-induced nausea and vomiting (CINV) for patients who receive high-dose cyclophosphamide, corticosteroids cannot be used during PTCy administration to exploit depletion of alloreactive T cells. Thus, CINV may not be adequately controlled in this situation. We retrospectively examined antiemetic efficacy of the combination of a 5-hydroxytryptamine-3 receptor antagonist (5-HT 3 RA) and a NK 1 receptor antagonist (NK 1 RA) in 36 patients who received PTCy, and compared this efficacy with that of the same combination together with dexamethasone in 27 patients conditioned with cyclophosphamide and total body irradiation (CY/TBI). The proportion of patients who had no vomiting during the acute phase of PTCy administration was 81%, and was lower than 100% in the CY/TBI group (p = 0.02). Our results suggest that prevention of CINV using 5-HT 3 RA and NK 1 RA during PTCy administration is suboptimal and that addition of antiemetic is necessary in patients who receive PTCy.

Background: High-dose myeloablative conditioning prior to autologous hematopoietic stem cell transplantation (autoHSCT) in pediatric patients is usually highly emetogenic. The antiemetic neurokinin-1 receptor antagonist fosaprepitant was safe and effective in children receiving highly emetogenic chemotherapy. Data on fosaprepitant during autoHSCT in children are currently not available., Methods: A total of 35 consecutive pediatric patients, who received an antiemetic prophylaxis with fosaprepitant (4 mg/kg; single dose, max. 1 x 150 mg/kg BW) and ondansetron (24-hours continuous infusion; 8-32 mg/24h) or granisetron (2 x 40 µg/kg∙d -1 ) during highly emetogenic conditioning chemotherapy before autoHSCT were retrospectively analyzed, and their results were compared with a control group comprising 35 consecutive pediatric patients, who received granisetron or ondansetron only. The antiemetic efficacy and the safety of the two prophylaxis regimens were compared with respect to three time periods after the first chemotherapy administration (0-24h, >24-120h, >120-240h)., Results: Clinical adverse events and clinically relevant increases/decreases of laboratory markers were similarly low and did not significantly differ between the two study groups ( p >0.05). The registered number of vomiting events was significantly higher in the control group in the time periods of 0-24h (64 vs 22 events; p <0.01), >24-120h (135 vs 78 events; p <0.0001), >120-240h (268 vs 105 events; p <0.0001), and the whole observation period 0-240h (467 vs 205 events; p <0.0001). The percentage of patients experiencing vomiting was higher in the control group during the time period of >24-120h (100% vs 74.3%) but not the other analyzed time periods ( p >0.05)., Conclusion: The fosaprepitant-based antiemetic prophylaxis was safe, well tolerated and significantly reduced vomiting in children undergoing highly emetogenic chemotherapy prior to autoHSCT. Prospective randomized trials are necessary to confirm these results., Competing Interests: All authors declare that they have no conflicts of interest., (© 2020 Cabanillas Stanchi et al.)

Background: Despite the availability of effective antiemetic regimens, patients still experience chemotherapy-induced nausea and vomiting (CINV). 5-Hydroxytryptamine 3 (5-HT3) receptor antagonists (RAs) are the mainstay of CINV prevention, and updated antiemetic guidelines include new options., Objective: The aim of this study was to highlight advances in CINV management, focusing on new 5-HT3 RA formulations in adults, updated antiemetic guidelines, and the role of nurses., Methods: MEDLINE searches were conducted for English-language publications for the past 15 years using relevant search terms ("serotonin receptor antagonist," "5-HT3 receptor antagonist," "antiemetic," "chemotherapy-induced nausea and vomiting") in the abstract or title. Abstracts at relevant major congresses for the past 3 years and additional pivotal publications were included. The most informative, relevant, and current publications were included., Results: 5-Hydroxytryptamine 3 RAs are effective in preventing acute (0-24 hours) CINV but less effective in the delayed phase (24-120 hours) given their short half-lives. Updated antiemetic guidelines include fixed-dose intravenous fosnetupitant and palonosetron (IV NEPA) and granisetron extended-release subcutaneous injection, a recently approved 5-HT3 RA formulation providing slow, controlled release of therapeutic granisetron concentrations for 5 days or longer. Nurses play a pivotal role in implementing updated guideline-recommended antiemetic regimens for highly and some moderately emetogenic chemotherapy regimens, comprising a 4- or 3-drug regimen of 5-HT3 RA, neurokinin-1 RA, and dexamethasone, with/without olanzapine., Conclusion: Newer antiemetic combinations and formulations provide flexibility for CINV prevention. Granisetron extended-release subcutaneous injection is a convenient subcutaneous granisetron option., Implications for Practice: Nurses play a critical role in understanding and using new antiemetic formulations and updated antiemetic guidelines in their practices.

Objective: Age-related cognitive decline, the deterioration in functions such as memory and executive function, is faced by most older adults and affects function and quality of life. No approved treatments exist for age-related cognitive decline. Computerized cognitive training has been shown to provide consistent albeit modest improvements in cognitive function as measured by neuropsychological testing. Vortioxetine, an antidepressant medication, has putative procognitive and proneuroplastic properties and therefore may be able to augment cognitive training. In this placebo-controlled study, the authors tested the cognitive benefits of vortioxetine added to cognitive training for adults age 65 or older with age-related cognitive decline., Methods: After a 2-week lead-in period of cognitive training, 100 participants were randomly assigned to receive either vortioxetine or placebo in addition to cognitive training for 26 weeks. The primary outcome measure was global cognitive performance, assessed by the NIH Toolbox Cognition Battery Fluid Cognition Composite. The secondary outcome measure was functional cognition, assessed by the UCSD Performance-Based Skills Assessment. All participants received motivational messaging and support from study staff to maximize adherence to the training., Results: Participants who received vortioxetine with cognitive training showed a greater increase in global cognitive performance compared with those who received placebo with cognitive training. This separation was significant at week 12 but not at other assessment time points. Both groups showed improvement in the secondary outcome measure of functional cognition, with no significant difference between groups., Conclusions: Vortioxetine may be beneficial for age-related cognitive decline when combined with cognitive training. These findings provide new treatment directions for combating cognitive decline in older adults.

A substantial proportion of cancer patients experience chemotherapy-induced nausea and vomiting (CINV) despite the use of antiemetic drugs. Prevalent genetic polymorphisms involved in antiemetic drug metabolism, drug transport and receptor pathways likely affect the effectiveness of antiemetics. Knowledge on which polymorphisms to integrate into individualised clinical care is needed. We did a systematic review evaluating the association between polymorphisms and effectiveness of antiemetics in cancer patients receiving moderately to highly emetogenic chemotherapy. Twenty studies n = 2331 evaluated eight polymorphisms in five candidate genes involved in 5-HT 3 antagonist pathways. HTR3C C1214G increased the risk of acute chemotherapy-induced vomiting in the dominant model (odds ratio (OR) = 2.67, 95 % confidence interval (CI): 1.08-6.63). ABCB1 C3435T reduced the risk of acute CINV in the recessive model (OR = 0.60, 95 % CI: 0.44-0.81). Future studies should evaluate candidate genes that affect pharmacogenetics of other antiemetics beside 5-HT 3 antagonists., Competing Interests: Declaration of Competing Interest Dr. TSUJI reports personal fees from Chugai Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd. and Nippon Kayaku Co., Ltd., outside the work of this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background We examined the efficacy of mirtazapine in preventing delayed nausea and vomiting following highly emetogenic chemotherapy (HEC). Patients and methods Patients who had experienced delayed emesis and would be subsequently scheduled for at least three more cycles of the same chemotherapy were randomly assigned to either a mirtazapine (15 mg daily on days 2-4) or a control group. In addition, both groups received a standard triplet regimen comprising aprepitant, a 5-HT3 receptor antagonist, and dexamethasone (7.5 mg on days 2-4). The chemotherapy regimens were either an epirubicin plus cyclophosphamide regimen or cisplatin-containing regimens. The primary end point was a complete response (no emesis and no rescue treatment) to the delayed phase (25-120 h post-chemotherapy) during Cycle 1. The impact on quality of life (QOL) was assessed using the Functional Living Index-Emesis (FLIE) questionnaire. Results Of 95 enrolled patients, 46 were assigned to the mirtazapine group and 49 to the control group. The complete response rate in the delayed phase during Cycle 1 was significantly higher with mirtazapine than in the control group (78.3% versus 49.0%, P = 0.003). The main adverse effects of mirtazapine were mild to moderate somnolence and weight gain. Mean total FLIE scores were similar between the two arms. Conclusions This is the first randomized prospective study to show that adding mirtazapine has a substantial and statistically significant benefit with good tolerance in patients with breast cancer who have experienced delayed emesis following the same prior HEC. (Trial registration: ClinicalTrials.gov NCT02336750).

L-3,4-dihydroxyphenylalanine (L-DOPA) has been the standard treatment for Parkinson's disease (PD), despite that its chronic use leads to motor fluctuations and dyskinesia in as many as 95% of patients. Previous studies have shown that serotonin type 3 (5-HT 3 ) receptor blockade reduces dopamine levels within the striatum, suggesting that it could potentially lead to a reduction of dyskinesia. Here, we assessed the effects of ondansetron on L-DOPA-induced abnormal involuntary movements (AIMs) in the 6-hydroxydopamine (6-OHDA)-lesioned rat. We performed two series of experiments. First, rats exhibiting stable AIMs were administered ondansetron (0.0001, 0.001, 0.01, 0.1 and 1 mg/kg) or vehicle in combination with L-DOPA, following which the effect of ondansetron on AIMs was assessed. In the second series of experiments, following 6-OHDA lesion, rats received daily administration of ondansetron (0.0001, 0.001 mg/kg) or vehicle, started concurrently with the first L-DOPA dose, and treatments were continued for 22 days. After a washout period, an acute L-DOPA challenge was administered and AIMs severity was assessed. The effect of ondansetron on L-DOPA anti-parkinsonian action was also determined. We found that the addition of ondansetron 0.0001 mg/kg to L-DOPA resulted in a significant reduction of AIMs severity (by 31%, P < 0.001), when compared to vehicle. Ondansetron 0.0001 mg/kg, when started concurrently with L-DOPA, also attenuated the development of AIMs, with AIMs being 64% less severe (P < 0.05), when compared to L-DOPA/vehicle. Ondansetron did not impair L-DOPA anti-parkinsonian action. Our results suggest that selective 5-HT 3 blockade is a promising strategy to reduce the severity of L-DOPA-induced dyskinesia and may also attenuate its development., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We performed a pooled analysis to evaluate the efficacy and adverse events (AEs) of olanzapine combined with dexamethasone plus 5-hydroxytryptamine type 3 receptor antagonist (5-HT3 RA) compared with 5-HT3 RA plus dexamethasone for the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in high and moderate emetogenic chemotherapy based on randomised controlled trials (RCTs). PubMed, EMBASE, Web of Science, the Cochrane Library, China Biomedical Literature database (CBM), WanFang Database, China National Knowledge Infrastructure (CNKI), and Chinese Science and Technology Periodical Database (VIP) (from their inception to April 2019) were searched to capture relevant articles. Relative risk with 95% confidence intervals for CINV and AEs were all extracted or calculated. Eleven studies with 1107 cancer patients were involved in this review. The pooled RR of delayed CINV (RR 0.50, 95% CI 0.38 to 0.66; p<0.01) were significantly decreased in the olanzapine group. The occurrence of insomnia was also statistically decreased, as was the rate of acute CINV (RR 0.60, 95% CI 0.48 to 0.75; p<0.01). However, only the percentages of CINV III and CINV IV were significantly decreased in the acute and delayed phases. Subgroup analysis demonstrated that the efficacy was not statistically significantly different between 5 mg and 10 mg olanzapine. Olanzapine significantly decreased the occurrence of CINV III and IV and insomnia in high and moderately emetogenic chemotherapy. Compared with 10 mg per day, 5 mg oral olanzapine may be more appropriate for patients with cancer., Competing Interests: Competing interests: None declared., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Confident relationships between diabetes andliver damagehave previously been established. This study was designed to evaluate hepaticinflammation, apoptosis, and endocannabinoid system alterations in diabetes with or withouttropisetrontreatment. Rats were assigned to five equal groups: control, tropisetron, diabetes, tropisetron+diabetes, and glibenclamide+diabetes (n = 7 in each group). Rats were treated with tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) as a positive control for two weeks after type 1 diabetes induction.Inflammatory cytokines tumor necrosis factor-alpha and interleukin 6 (TNF-α and IL-6) levels, apoptotic cells, and fatty acid amide hydrolase (FAAH) enzyme, at both transcriptional and protein levels increased, while the gene expression of cannabinoid receptor 1 (CB1) and its protein level decreased in the diabetic liver compared to the control. Treatment with tropisetron reversed TNF-α, apoptotic index, and endocannabinoid system components. These effects were equipotent with glibenclamide, indicating that tropisetroncan protect liver tissue against diabetic disturbances. These findings strongly support the idea that diabetes-induced liver abnormality is mediated by inflammatory reactions, apoptosis, and endocannabinoid system, and that these effects can be alleviated by using tropisetron as an antioxidant and anti-inflammatory agent., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cisplatin is classified as a drug with high emetic risk; thus, the use of aprepitant or fosaprepitant in addition to a 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonist and dexamethasone is recommended for antiemetic therapy. Further, hydration is required to prevent renal dysfunction, and the use of magnesium has been proposed as a part of the hydration procedure. When fosaprepitant is chosen for antiemetic therapy because the patient has dysphagia, and magnesium is added to the hydration procedure, there may be an incompatibility between the two drugs that reduces the antiemetic effect. In our hospital, in a former regimen, these two drugs were administered concurrently as premedication for regimens containing cisplatin. We varied the conditions so that in a revised regimen the two drugs did not come into contact due to pharmaceutical support, and we conducted a retrospective study to determine the difference in the antiemetic effect. The observation period was 2 years (from October 2015 to September 2017) for the former regimen group (n = 89) and 2 years (from October 2017 to September 2019) for the revised regimen group (n = 177). Comparison of the former and revised regimen groups revealed sex (p = 0.012); anticancer drug dosage (p = 0.006); and variation of premedication condition (p = 0.043) as factors affected by the revised regimen. Optimization of the premedication regimen was a form of necessary pharmaceutical support to maintain the patient's QOL.

Maternal hemodynamics, positioning, and anesthesia technique for cesarean delivery influence neonatal acid-base balance; direct effects from drugs that cross the placenta also have an influence. Spinal anesthesia limits fetal exposure to depressant drugs and avoids maternal airway instrumentation, but is associated with hypotension. Hypotension may be prevented/treated with vasopressors and intravenous fluids. Current evidence supports phenylephrine as the first-line vasopressor. Fifteen degrees of lateral tilt during cesarean delivery has been advocated to relieve vena caval obstruction, but routine use may be unnecessary in healthy nonobese women having elective cesarean delivery if maternal blood pressure is maintained near baseline., (Copyright © 2019 Elsevier Inc. All rights reserved.)