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Abstract 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/ .

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/. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to evaluate the efficacy and safety of azasetron compared to ondansetron in the prevention of delayed chemotherapy-induced nausea and vomiting. Materials and Methods: This study was a multi-center, prospective, randomized, double-dummy, double-blind and parallel-group trial involving 12 institutions in Korea between May 2005 and December 2005. A total of 265 patients with moderately and highly emetogenic chemotherapy were included and randomly assigned to either the azasetron or ondansetron group. All patients received azasetron (10 mg intravenously) and dexamethasone (20 mg intravenously) on day 1 and dexamethasone (4 mg orally every 12 hours) on days 2-4. The azasetron group received azasetron (10 mg orally) with placebo of ondansetron (orally every 12 hours), and the ondansetron group received ondansetron (8 mg orally every 12 hours) with placebo of azasetron (orally) on days 2-6. Results: Over days 2-6, the effective ratio of complete response in the azasetron and ondansetron groups was 45% and 54.5%, respectively (95% confidence interval, -21.4 to 2.5%). Thus, the non-inferiority of azasetron compared with ondansetron in delayed chemotherapy-induced nausea and vomiting was not proven in the present study. All treatments were well tolerated and no unexpected drug-related adverse events were reported. The most common adverse events related to the treatment were constipation and hiccups, and there were no differences in the overall incidence of adverse events. Conclusion: In the present study, azasetron showed inferiority in the control of delayed chemotherapy- induced nausea and vomiting compared with ondansetron whereas safety profiles were similar between the two groups. [ABSTRACT FROM AUTHOR]

The aim of the present study was to develop a transdermal drug delivery system for azasetron and evaluate the correlation between in vitro and in vivo release. The effects of different adhesives, permeation enhancers, and loadings of azasetron used in patches on the penetration of azasetron through rabbit skin were investigated using two-chamber diffusion cells in vitro. For in vivo studies, azasetron pharmacokinetic parameters in Bama miniature pigs were determined according to a noncompartment model method after topical application of transdermal patches and intravenous administration of azasetron injections. The best permeation profile was obtained with the formulation containing DURO-TAK 87-9301 as adhesive, 5% of isopropyl myristate as penetration enhancer, and 5% of azasetron. The optimal patch formulation exhibited sustained release profiles in vivo for 216 h. The in vivo absorption curve in Bama miniature pigs obtained by deconvolution approach using WinNonlin® program was correlated well with the in vitro permeation curve of the azasetron patch. These findings indicated that the developed patch for azasetron is promising for the treatment of delayed chemotherapy-induced nausea and vomiting, and the in vitro skin permeation experiments could be useful to predict the in vivo performance of transdermal azasetron patches. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:4540-4548, 2012 [ABSTRACT FROM AUTHOR]

A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine azasetron concentrations in pig plasma. After addition of granisetron as internal standard (IS), plasma samples were deproteinized with methanol. The post-treatment samples were analyzed on a Diamonsil C18 column interfaced with a triple quadrupole tandem mass spectrometer in positive electrospray ionization mode. Methanol-5 mmol/l ammonium acetate-formic acid (45:55:0.3, v/v/v) was used as the isocratic mobile phase at a flow rate of 0.5 ml/min. The assay was linear over the concentration range of 0.25-200 μg/l. The intraand inter-day precision was within 12.1% in terms of relative standard deviation (RSD%) and the accuracy within 8.3% in terms of relative error. This simple and sensitive LC-MS/MS method with short analytical time (6.5 min each sample) was successfully applied to the pharmacokinetic study of azasetron in Bama miniature pigs after a transdermal administration of 4.0 mg/kg azasetron hydrochloride. [ABSTRACT FROM AUTHOR]

Purpose: We compared the prophylactic effects of intravenously administered azasetron (10 mg) and ondansetron (8 mg) on postoperative nausea and vomiting (PONV) in patients undergoing gynecological laparoscopic surgery under general anesthesia. Materials and Methods: We studied 98 ASA physical status I or II 20-65 years old, female patients, in this prospective, randomized, double blind study. Patients were randomly divided into two groups and received ondansetron 8 mg (group 0) or azasetron 10 mg (group A) 5 mm before the end of surgery. The incidence of PONY, Visual Analogue Scale (VAS) for pain, need for rescue antiemetic and analgesics, and adverse effects were checked at 1, 6, 12, 24, and 48 h postoperatively. Results: The overall incidence of PONY was 65% in group 0 and 49% in group A. The incidence of PONY was significantly higher in group 0 than in group A at 12-24 h postoperatively (nausea; 24% vs. 45%, p = 0.035, vomiting; 2% vs. 18%, p = 0.008), but there were no significant differences at 0-1, 1-6, 6-12 or 24-48 h. Conclusion: In conclusion, azasetron (10 mg) produced same incidence of PONV as ondansetron (8 mg) in patients undergoing general anesthesia for gynecological laparoscopic surgery. Azasetron was more effective, in the intermediate post-operative period, between 12 and 24 h. [ABSTRACT FROM AUTHOR]

Abstract: Repeated intermittent administration of psychostimulants causes behavioral sensitization in rodents. Previous studies using serotonin (5-HT) receptor ligands show that the 5-HT system is involved in cocaine-induced behavioral sensitization in rats, but the role of the 5-HT system has not been studied in mice. The present study examined the effects of the 5-HT1A receptor agonist osemozotan, the 5-HT2 receptor antagonist ritanserin and the 5-HT3 receptor antagonist azasetron on cocaine-induced behavioral sensitization in male ddY mice. Repeated administration of cocaine for 7 days enhanced cocaine-induced locomotor activity, and this sensitization was observed even after withdrawal for 7–14 days. Cocaine-induced behavioral sensitization after a 7-day withdrawal was significantly reduced with the coadministration of osemozotan, ritanserin or azasetron with cocaine repeatedly for 7 days. A single injection of osemozotan or ritanserin before cocaine challenge also reduced repeated cocaine-induced behavioral sensitization. However, none of these ligands inhibited cocaine-induced behavioral sensitization, when each drug was administered for 7 days after repeated cocaine administration. These results suggest that the central 5-HT system plays a role in the development and expression, but not maintenance, of behavioral sensitization in cocaine-treated mice. [Copyright &y& Elsevier]

1 Experiments were carried out in conscious, chronically instrumented, male, Sprague-Dawley rats to delineate the regional haemodynamic effects of the putative endogenous cannabinoid, anandamide, (0.075-3 mg kg[sup-1]), and to dissect some of the mechanisms involved. 2 At all doses of anandamide, there was a significant, short-lived increase in mean arterial blood pressure associated with vasoconstriction in renal, mesenteric and hindquarters vascular beds. 3 The higher doses (2.5 and 3 mg kg[sup-1]), caused an initial, marked bradycardia accompanied, in some animals, by a fall in arterial blood pressure which preceded the hypertension. In addition, after the higher doses of anandamide, the hindquarters vasoconstriction was followed by vasodilatation. 4 Although some of the effects described above resembled those of 5-HT (25 μg kg[sup-1]), the bradycardia and hypotensive actions of the latter were abolished by the 5HT[sub3]-receptor antagonist, azasetron, whereas those of anandamide were generally unaffected. 5 None of the cardiovascular actions of anandamide were influenced by the CB[sub1]-receptor antagonist, AM 251, but its bradycardic effect was sensitive to atropine. and its hindquarters vasodilator action was suppressed by the β[sub2]-adrenoceptor antagonist, ICI 118551. 6 The results differ, in several aspects, from those previously reported in anaesthetized animals, and underscore the important impact anaesthesia can have on responses to anandamide. [ABSTRACT FROM AUTHOR]

Combination antiemetic therapy has become common practice for the prevention of nausea and vomiting caused by anticancer drugs. In this study, we investigated the stability of azasetron hydrochloride 0.1 mg/mL plus dexamethasone sodium phosphate 0.05, 0.1, or 0.2 mg/mL in 0.9% sodium chloride injection and stored in polyolefin bags and glass bottles over a period of 14 days at 4°C and 48 hours at 25°C. The stability studies were evaluated by visual inspection, pH measurement, and a high-pressure liquid chromatography assay of drug concentrations. During the study period, the concentration of each drug in the various solutions remained above 97% of the initial concentration at both 4°C and 25°C when protected from room light. Under the condition of 25°C with exposure to room light, the concentrations of both drugs were significantly lowered over 48 hours. The pH value decreased, and the color changed from colorless to pink. Our study demonstrates that the azasetron-dexamethasone mixture at a clinically relevant concentration seems to be stable for 48 hours at 25°C and for 14 days at 4°C when packaged in polyolefin bags or glass bottles and protected from room light. The room light is the main influential factor on stability. Clinicians should be aware that combinations of azasetron hydrochloride and dexamethasone sodium phosphate in solution with light exposure should be avoided., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

Purpose: We compared the prophylactic effects of intravenously administered azasetron (10 mg) and ondansetron (8 mg) on postoperative nausea and vomiting (PONV) in patients undergoing gynecological laparoscopic surgery under general anesthesia., Materials and Methods: We studied 98 ASA physical status I or II 20-65 years old, female patients, in this prospective, randomized, double blind study. Patients were randomly divided into two groups and received ondansetron 8 mg (group O) or azasetron 10 mg (group A) 5 min before the end of surgery. The incidence of PONV, Visual Analogue Scale (VAS) for pain, need for rescue antiemetic and analgesics, and adverse effects were checked at 1, 6, 12, 24, and 48 h postoperatively., Results: The overall incidence of PONV was 65% in group O and 49% in group A. The incidence of PONV was significantly higher in group O than in group A at 12-24 h postoperatively (nausea; 24% vs. 45%, p = 0.035, vomiting; 2% vs. 18%, p = 0.008), but there were no significant differences at 0-1, 1-6, 6-12 or 24-48 h., Conclusion: In conclusion, azasetron (10 mg) produced same incidence of PONV as ondansetron (8 mg) in patients undergoing general anesthesia for gynecological laparoscopic surgery. Azasetron was more effective, in the intermediate post-operative period, between 12 and 24 h.