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Cannabis Use Disorder (CUD) has no FDA-approved treatment. Serotonin-2c (5HT2c) agonists have preclinical and human laboratory evidence for their potential efficacy for CUD. We assessed the tolerability and effects of lorcaserin (5HT2c agonist) on CUD. In a 10-week, open label, uncontrolled trial, the tolerability of lorcaserin was tested in outpatients with CUD. Adverse events (AE) were assessed weekly. Cannabis use was assessed twice weekly by the Timeline follow-back and quantitative urine metabolites. Seventeen participants enrolled, and 14 received medication. Participants' average age was 35 years; majority were male (N = 12). The medication was well tolerated in males. There were no serious adverse events (SAE). The most common AE's were headache/migraine (N = 4, all females), anorexia (N = 3), and irritability (N = 2). Participants decreased their frequency of cannabis use significantly (p < 0.001), adjusted for baseline use. By the end of the trial, participants decreased by 1.76 (SE = 0.47) cannabis using days/week. Average daily amount of cannabis and urine THC metabolite levels did not change significantly. Lorcaserin was well tolerated in males but not females, suggesting possible sex differences. Future trials of other 5HT2c agonists (lorcaserin was withdrawn at the request of the FDA) should consider longer dose titration phases. [ABSTRACT FROM AUTHOR]

Ergot alkaloids, a class of mycotoxins associated with ergotism, act as agonists on serotonin (5HT) receptors, specifically 5HT2a, which mediate smooth muscle contraction and vasoconstriction. The objective of this study was to examine the impact of ergot alkaloid exposure during mid and late gestation on microscopic placental structure and vascular development. Ewes were fed endophyte-infected tall fescue seed containing ergot alkaloids (E+/E+, 1.77 mg ewe−1 d−1) or endophyte-free tall fescue seed (E-/E-, 0 mg ergot alkaloids) during both mid (d 35 to d 85) and late gestation (d 86 to d 133). On d 133 of gestation, a terminal surgery was performed and two placentomes of the type B morphology were collected for microscopic analyses. Amorphous connective tissue regions were larger (p < 0.0001) and more numerous (p = 0.025) in the placentome of ergot alkaloid exposed ewes. Staining showed no difference (p = 0.83) in the number of vessels present, but luminal area of maternal vasculature was 117% greater (p < 0.0001) in ergot alkaloid exposed ewes. Results showed that exposure to ergot alkaloids during gestation slowed maturation of the fetal villi as indicated by greater amorphous connective tissue regions, and altered size and shape of blood vessels to counteract reductions in blood flow caused by vasoconstriction. [ABSTRACT FROM AUTHOR]

Background: Lasmiditan is a selective serotonin (1F) receptor agonist approved for acute treatment of migraine with 3 doses: 50, 100, and 200 mg.Objective: To help provide dosing insights, we assessed the efficacy and safety of lasmiditan in patients who treated two migraine attacks with the same or different lasmiditan doses.Methods: Integrated analyses used data from the migraine attack treated in either of two controlled, Phase 3, single attack studies (SAMURAI/SPARTAN), and after the first attack treated in the open-label GLADIATOR extension study. Eight patient groups were created based on the initial dose received in SAMURAI or SPARTAN and the subsequent dose in GLADIATOR: placebo-100, placebo-200, 50-100, 50-200, 100-100, 100-200, 200-100, 200-200. Migraine pain freedom, migraine-related functional disability freedom, most bothersome symptom (MBS) freedom, and pain relief were evaluated at 2-h post-dose. The occurrence of most common treatment-emergent adverse events (MC-TEAE) was evaluated. Shift analyses were performed for pain freedom and ≥1 MC-TEAE. The incidence of patients with a specific outcome from the first and subsequent doses were compared within each dose change group using McNemar's test.Results: Small, but consistent, increases in incidences of pain freedom, migraine-related functional disability freedom, MBS freedom, and pain relief occurred when the second lasmiditan dose was higher than the initial dose. For patients starting on 50 mg, increasing to 100 or 200 mg provided a positive efficacy-TEAE balance, despite an increase in incidence of ≥1 MC-TEAE. For patients starting on 100 mg, increasing to 200 mg provided a positive efficacy-TEAE balance. If the initial dose was 100 or 200 mg, the incidence of patients experiencing ≥1 MC-TEAE decreased or stayed the same with their subsequent dose, regardless of dose. Decreasing from 200 to 100 mg led to a decrease in patients with pain freedom and ≥1 MC-TEAE, resulting in a neutral efficacy-TEAE balance. Shift analyses supported these findings.Conclusion: A positive efficacy-TEAE balance exists for patients increasing their lasmiditan dose for treatment of a subsequent migraine attack. These results could be important for optimizing dosing for individual patients.Clinicaltrials.gov: SAMURAI (NCT02439320); SPARTAN (NCT02605174); GLADIATOR (NCT02565186). [ABSTRACT FROM AUTHOR]

Current theory suggests that aggressive behavior in the crayfish is largely modulated and regulated by the neurotransmitter serotonin (5-HT). To test this theory that links serotonin to aggression, we performed a series of drug treatments using various serotonin-related chemicals to measure their effects on subsequent aggressive behavior. Treatments included serotonin, the serotonin precursor tryptophan, agonists: 1-(3-chlorophenyl) piperazine (m-CPP) and 5-Carboxy, an antagonist: cinanserin, and a serotonin receptor specific neurotoxin: 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT). Significant increases in aggression of Faxonius rusticus crayfish were observed when injected with serotonin and both agonists, however no decrease in aggression occurred with the antagonist. Crayfish injected with the agonist m-CPP increased aggression but did not directly confer success in fights. Our data support the current literature that the internal aggressive state of crayfish is altered by serotonin and its agonist/antagonists, however it does not on its own improve the aggressive fighting response and/or dominance status. [ABSTRACT FROM AUTHOR]

Objective: This study was aimed at examining the epileptiform activity of the 5-HT2 serotonin receptor agonist and antagonist, and 5-hydroxytryptophan (5-HTP) in penicillin-induced epilepsy in albino Wistar rats. Methods: For this purpose, 90 albino male Wistar rats were used in this study. Epileptiform activity was induced by an injection of penicillin, an agonist of GABAA receptor, (500 IU, i.c.) into the somatomotor cortex. Thirty minutes after the injection of penicillin, 2,5-dimethoxy-4-iodoamphetamine (DOI, an agonist of 5-HT2 receptor) (0.5, 1, 2 and 4 mg/kg, i.p.), methysergide, an antagonist of 5-HT2 receptor, (1, 10, 20, 50 and 100 µM, i.c.v.) and 5-HTP, precursor of 5-HT, (25, 50, 75 and 100 mg/kg, i.p.) were administered, respectively. Results: DOI, at the doses of 1 and 2 mg/kg, significantly decreased penicillin-induced epileptiform activity (p < 0.05). Methysergide, at the doses of 20, 50 and 100 µM, significantly increased the mean spike frequency of penicillin-induced epileptiform activity (p < 0.05). The doses of 50, 75 and 100 mg/kg of 5-HTP decreased the mean spike frequency of penicillin-induced epileptiform activity (p < 0.05). The mean of amplitude of penicillin-induced epileptiform activity did not significantly change in any of the groups (p > 0.05). Conclusion: The electrophysiological data from the present study suggest that serotonin 5-HT2 receptors have an important role in controlling penicillin-induced epileptiform activity in the rat. [ABSTRACT FROM AUTHOR]

The medications in use for treating migraine are directed either towards inhibiting the characteristic migraine pain or towards preventing it from occurring. In this pursuit, ergotamine and sumatriptan class of 5-HT1B receptor agonists have been proved to be extremely effective. Further research into this field led us to design cyanopyridone derivatives that were synthesized through cyclization of 2-cyano-N-phenylacetamides with malonitrile and 2,3-dihydrobenzo[b][1,4]dioxine-6-carbaldehyde. The synthesized cyanopyridones analogs, when docked with active site of 5-HT1B receptor, showed better binding affinity compared to standard antimigraine medications. Additionally, in silico ADME prediction for drug-likeness and pharmacokinetics revealed that all compounds are safer and can be used as antimigraine medicine. The structure of the synthesized compounds has been elucidated on the basis of spectral analysis. [ABSTRACT FROM AUTHOR]

Objectives: Bowel cleansing is a major patient complaint during colonoscopy. Adding laxatives to the bowel preparation is effective in replacing a portion of bowel preparation solution and reducing its volume. Prucalopride is a serotonin receptor agonist that stimulates gastrointestinal motility and provides propulsive force for defecation. This study aimed to compare 1 L polyethylene glycol (PEG) with ascorbic acid (Asc) plus 2mg prucalopride (1LP/AP) and 2 L PEG with Asc (2LP/A) for colonoscopy preparation with respect to bowel-cleansing quality and side effects. Methods: A single-center, randomized, prospective study was conducted with 260 outpatients administered either 1LP/AP or 2LP/A. The primary endpoint was bowel preparation quality, which was evaluated using the Boston Bowel Preparation Scale and Aronchick Bowel Preparation Scale, and the secondary endpoints were patient tolerability and acceptability, assessed by a questionnaire-based survey. Results: The adequate bowel preparation rates were 88.5% and 83.1% in the 2LP/A and 1LP/AP groups, respectively, and the efficacy of 1LP/AP was equivalent to the control regimen (p=.216). Other colonoscopic variables including adenoma detection rate were similar in both groups. Patient tolerability and acceptability were not significantly different, but patients in the 1LP/AP group were more willing to repeat the same regimen (p=.039). Conclusions: Bowel preparation quality with 1LP/AP was equivalent to that with 2LP/A, which did not increase the occurrence of side effects, but it reduced the volume of the solution ingested, and increased patient satisfaction. [ABSTRACT FROM AUTHOR]

The article discusses some of the controversies over psychedelic drugs in managing a variety of psychiatric disorders. The discovery of lysergic acid diethyamide, or LSD, was said to be a strong contributor to the neuroscientific model that took hold in the 1950s and 1960s. Some investigators in Europe and the U.S. re-initiated human studies with psychedelics during the 1990s. It is noted that the mechanisms underlying psychedelic efficacy might be biological and psychological.

Humans have used serotonergic hallucinogens (i.e. psychedelics) for spiritual, ceremonial, and recreational purposes for thousands of years, but their administration as part of a structured therapeutic intervention is still a relatively novel practice within Western medical and psychological frameworks. In the mid-20th century, considerable advances were made in developing therapeutic approaches integrating administration of low (psycholytic) and high (psychedelic) doses of serotonergic hallucinogens for treatment of a variety of conditions, often incorporating psychoanalytic concepts prevalent at that time. This work contributed seminal insights regarding how these substances may be employed with efficacy and safety in targeted therapeutic interventions, including the importance of optimizing set (frame of mind) and setting (therapeutic environment). More recently, clinical and pharmacological research has revisited the effects and therapeutic potential of psychedelics utilizing a variety of approaches. The current article provides an overview of past and present models of psychedelic therapy, and discusses important considerations for future interventions incorporating the use of psychedelics in research and clinical practice. [ABSTRACT FROM AUTHOR]

Serotonin (5-hydroxytryptamine, 5-HT)2A receptor agonists have recently emerged as promising new treatment options for a variety of disorders. The recent success of these agonists, also known as psychedelics, like psilocybin for the treatment of anxiety, depression, obsessive-compulsive disorder (OCD), and addiction, has ushered in a renaissance in the way these compounds are perceived in the medical community and populace at large. One emerging therapeutic area that holds significant promise is their use as anti-inflammatory agents. Activation of 5-HT2A receptors produces potent anti-inflammatory effects in animal models of human inflammatory disorders at sub-behavioural levels. This review discusses the role of the 5-HT2A receptor in the inflammatory response, as well as highlight studies using the 5-HT2A agonist (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] to treat inflammation in cellular and animal models. It also examines potential mechanisms by which 5-HT2A agonists produce their therapeutic effects. Overall, psychedelics regulate inflammatory pathways via novel mechanisms, and may represent a new and exciting treatment strategy for several inflammatory disorders. [ABSTRACT FROM AUTHOR]

This article provides a clinically relevant review of the first medication approved by the US Food and Drug Administration for hypoactive sexual desire disorder (HSDD) in premenopausal women. In this short piece, the human sexual response cycle and its relevance to HSDD will be described as well as the pharmacological mechanism of action of flibanserin. Finally, efficacy and safety data of this new medication will be summarised. [ABSTRACT FROM PUBLISHER]

Twenty-four gramine derivatives were synthesized and evaluated on MT1and 5-HT1Areceptorsin vitro. Among them, seven derivatives (7,8,16,19,20,21,and24)exhibited higher agonisting activities on MT1or 5-HT1Areceptors. Compared with gramine, derivatives7,8,16,19,20,21,and24displayed 1.6–3.5-fold increase in agonistic rates on 5-HT1Areceptor. Particularly, derivatives7,19,and21exhibited significant agonistic activities on MT1and 5-HT1Areceptors with EC50values of 0.51, 0.39, 0.50 mΜ and 0.28, 0.46, 0.23 mΜ, respectively. The preliminary structure–activity relationships of gramine derivatives were summarized for further investigation on MT1and 5-HT1Areceptors as new potential agonists. [ABSTRACT FROM PUBLISHER]

Objectives: Lorcaserin is a serotonin 2C receptor agonist approved for chronic weight management. This analysis explores the number of patients needed to be treated (NNT) with lorcaserin for one more patient to achieve weight loss and glycemic goals.Methods: This is a post hoc analysis of three Phase 3 studies in adults with and without type 2 diabetes mellitus (T2DM) treated with lorcaserin 10 mg BID or placebo. NNT is reported for patients achieving ≥5% or ≥10% weight loss, achievement of either HbA1c <5.7% or FPG <100 mg/dL in patients with prediabetes, and reduction of HbA1c to <7% in patients with T2DM at Week 52.Results: In the modified intention-to-treat (MITT) population, NNTs for ≥5% and ≥10% weight loss were 3.6 and 6.2 (without T2DM) and 4.3 and 7.5 (with T2DM); in Week 12 responders (≥5% weight loss at Week 12), NNTs were 1.7 and 2.6 (without T2DM) and 1.9 and 3.2 (with T2DM). In patients with prediabetes, NNTs to achieve HbA1c <5.7% were 9.9 (MITT) and 5.2 (Week 12 responders). In patients with T2DM, NNTs to achieve HbA1c <7% were 4.2 (MITT) and 2.3 (Week 12 responders).Conclusion: In addition to weight management, lorcaserin improved glycemic control in patients with prediabetes and facilitated targeted HbA1c reduction in patients with T2DM, especially for those who achieved ≥5% weight loss by Week 12. Assessment of treatment response at Week 12 is a valuable tool to achieve efficient use of healthcare resources.Clinical Trial Registration: www.clinicaltrials.gov identifiers are NCT00395135, NCT00603291, and NCT00603902. [ABSTRACT FROM AUTHOR]

Objectives: Lorcaserin is a selective 5-HT2C (5-hydroxytryptamine 2C) receptor agonist indicated for weight management. Here, we assess the impact of lorcaserin on progression from prediabetes to type 2 diabetes (T2D) and on reversion from prediabetes to euglycemia.Methods: This is a post hoc analysis of pooled data from two Phase 3 studies, BLOOM and BLOSSOM (N = 6136), evaluating the impact of lorcaserin on weight and glycemic parameters over 52 weeks in the subpopulation of obese/overweight subjects with prediabetes, alternately defined by fasting plasma glucose (FPG) 100-125 mg/dl or glycated hemoglobin (HbA1c) 5.7-6.4% at baseline.Results: At Week 52, in the subpopulation with prediabetes, nearly twice as many lorcaserin-treated subjects achieved ≥5% weight loss versus placebo (HbA1c: 55.6% vs. 27.5%, p < 0.001; FPG: 52.8% vs. 28.8%, p < 0.001), and a significantly lower percentage of lorcaserin-treated subjects progressed to T2D versus placebo based on HbA1c (lorcaserin 3.2%, placebo 5.0%, p = 0.032) but not FPG (lorcaserin 1.6%, placebo 2.6%, p = 0.227). A significantly greater proportion of lorcaserin-treated subjects versus placebo also reverted to euglycemia based on both HbA1c (lorcaserin 40%, placebo 29.5%, p < 0.001) and FPG (lorcaserin 52.4%, placebo 46.5%, p = 0.047).Conclusion: In subjects with prediabetes, lorcaserin may contribute to weight loss and improve glycemic parameters, and thus may help with preventing progression to T2D and promoting reversion to euglycemia.Clinical Trial Registration: www.clinicaltrials.gov identifiers are NCT00395135 (BLOOM) and NCT00603902 (BLOSSOM). [ABSTRACT FROM AUTHOR]

Lorcaserin is a selective 5-hydroxytryptamine receptor 2c agonist developed as a weight-loss drug. Phase II and III clinical trials support lorcaserin as not only reducing adiposity (i.e., fat mass), but also as improving the metabolic diseases commonly associated with adiposopathy (i.e., fat dysfunction). At the time of this writing, regulatory processes continue towards evaluating lorcaserin as a potentially marketed weight-loss and weight-maintenance agent. Some of the challenges facing lorcaserin are similar to the difficulties encountered by all investigational weightloss therapeutic agents, which include evolving paths towards approval. While important for clinicians to understand approval hurdles for all therapeutics, it is especially critical for researchers and developers to grasp the unique regulatory complexities of anti-obesity agents. This article profiles lorcaserin as an illustrative example of general drug development regulatory processes, and specifically details the unique challenge of weight-loss drug development. INSETS: Key issues;Summary of US FDA criteria for drug development and approval.. [ABSTRACT FROM AUTHOR]

Despite the large body evidence from a variety of studies, the role of the serotonergic projection in the circadian system is still unclear. Previous work suggested that 5-HT is involved in both the response of SCN neurons to light and the phase-resetting properties of nonphotic stimuli. In hamsters, short exposure to constant light potentiates circadian phase-shifting caused by nonphotic stimuli, and the 5-HT pathway may be connected with this effect. The aim of this study was to determine whether a similar effect obtains in mice. We examined brief light-potentiation of (R)-(+)-8-OH-DPAT (8-hydroxyl-2-[di-n-propyloamino]-tetralin) and WAY100635 phase resetting, and found that short constant light before administration of (R)-(+)-8-OH-DPAT significantly enhanced the delays of the phase shift of the locomotor activity rhythm as compared with NaCl-injected animals. The transition from short LL to DD caused a phase shift, and WAY100635 attenuated this effect. [ABSTRACT FROM AUTHOR]

Rizatriptan benzoate is a recently developed antimigraine drug used for the treatment of migraines and severe headaches. In the synthesis of rizatriptan benzoate in bulk,various impurities are formed. The present work details the development of a simple and novel process for the preparation of hydrazone impurity (6), rizatriptan N-oxide (7), rizatriptan dimer (9), desmethyl rizatriptan (13), 5-(1H-1,2,4-triazol-1-yl-methyl)-1H-indole-3-ethanamine hydrochloride (14), N-methyl rizatriptan oxalate (15), and impurities. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of oral almotriptan 12.5 mg as an acute treatment for migraine with a focus on triptan-experienced versus triptan-naïve patients.Research design and methods: Four recent Almirall-sponsored clinical trials of oral almotriptan 12.5 mg in acute migraine, in which data regarding previous acute therapy were collected, are reviewed. The results and conclusions are limited by the open-label and post hoc design of some of these trials and analyses.Results: In two trials, almotriptan 12.5 mg was used to treat migraine sufferers who were dissatisfied with or were receiving inadequate results with their previous therapy. One of these trials enrolled only patients whose dissatisfaction with their current therapy was confirmed by a validated questionnaire; the other looked at almotriptan 12.5 mg efficacy in patients with previous poor response to sumatriptan. In the other two trials, patients had been achieving satisfactory results with their migraine therapy; one was a randomized, double-blind clinical trial of almotriptan 12.5 mg and zolmitriptan 2.5 mg, the other was an open-label almotriptan 12.5 mg satisfaction trial. Almotriptan 12.5 mg is shown to be effective, well-tolerated, and preferred to previous agents in both patients who were satisfied with, and those who were dissatisfied with, their previous therapy.Conclusions: Almotriptan should, therefore, not only be considered as first-line therapy for acute migraine but should also be considered for patients who are not satisfied with or not receiving optimal relief from their current acute therapy. [ABSTRACT FROM AUTHOR]

Sumatriptan is the first serotonin (5-hydroxytryptamine [5-HT]1B/1D) receptor agonist specifically designed for the acute treatment of migraine. A new sumatriptan fast disintegrating/rapid release tablet (FDT/RRT) using RT technology™ has been developed to enhance tablet disintegration and dispersion in the stomach with the intention of speeding absorption and onset of effect, hence mitigating the effects on the gastrointestinal dysmotility that typically accompanies the attack. Sumatriptan FDT/RRT is bioequivalent to conventional tablets, although it provides slightly faster absorption during early post-dose interval. Clinical trials indicate that sumatriptan FDT/RRT is rapidly effective in terms of freedom from pain and return to normal activities, both with early and late treatment. The drug is well tolerated. In an oral formulation, which is the patients' preferred dosing route, sumatriptan FDT/RRT may therefore constitute an advance in the management of acute migraine attacks. [ABSTRACT FROM AUTHOR]

Eletriptan is a second-generation 5-hydroxytryptamine1B/1D receptor agonist, or triptan, indicated for the acute treatment of migraine. Eletriptan has a favorable pharmacokinetic and pharmacodynamic profile expressed by bioavailability, half-life and high selectivity for cranial arteries. It has been shown to be effective and well tolerated in a wide preapproval development program, which included over 11,000 patients and treated more than 74,000 migraine attacks. In clinical trials, eletriptan has been demonstrated to be one of the most effective oral therapies for the acute treatment of migraine and has shown a very high safety and tolerability profile across the studies performed. Eletriptan showed the most favorable cost-effectiveness profile when compared with other agents in its class. [ABSTRACT FROM AUTHOR]

Objective . To evaluate the impact of an intensive pharmaceutical care campaign targeting inappropriate use of triptans. Design. Randomized controlled trial. Setting . 22 community pharmacies in the County of Funen, Denmark. Subjects . A total of 1123 triptan users at intervention pharmacies and 1340 at control pharmacies. Intervention . Intervention pharmacy staff received information on migraine and other types of headache, detection of inappropriate triptan use and other drug-related problems, and techniques for establishing a dialogue with patients. Intervention consisted of a folder and a structured dialogue with the pharmacy staff. The folder included questions aimed at detecting overuse and inappropriate triptan use. Main outcome measures . Change in average triptan consumption in doses per month measured by means of a prescription database with information on all purchases of reimbursed drugs at the level of the individual patient. Results . Overall, intervention had no statistically significant short-term impact on patients’ consumption of triptans either among incident users (intervention/control ratio 1.02; 95% confidence interval 0.95 to 1.12), or among prevalent users (1.02; 0.97 to 1.08). No effects were observed after 6 and 9 months, apart from a possible borderline effect after 9 months among prevalent users with intermediate triptan consumption (0.93; 0.87 to 1.00). Conclusion . The pharmaceutical care campaign did not reduce the use of triptans. [ABSTRACT FROM AUTHOR]

Background: Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western and Asia-Pacific populations. This study evaluated the efficacy, safety and tolerability of tegaserod versus placebo in patients with IBS. Methods: Patients with IBS (excluding those whose primary bowel symptom was diarrhoea) were randomized to receive either tegaserod 6 mg b.i.d. ( n = 327) or placebo ( n = 320) for a 12-week double-blind treatment period. The primary efficacy variable (over weeks 1 to 4) was the response to the question: 'Over the past week do you consider that you have had satisfactory relief from your IBS symptoms?' Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and the individual IBS symptoms. Results: Overall satisfactory relief was greater in the tegaserod group than in the placebo group. Over weeks 1 to 4, the odds ratio was 1.54, that is, the odds of satisfactory relief were 54% higher in the tegaserod group than in the placebo group (95% confidence interval for odds ratio (CI) (1.14, 2.08), P = 0.0049). Over weeks 1 to 12, the odds ratio was 1.78, that is, the odds of satisfactory relief were 78% higher in the tegaserod group than in the placebo group (95% CI (1.35, 2.34), P < 0.0001). A statistically significant therapeutic gain over placebo was observed for the majority of weeks from week 1 to week 12 (except weeks 1 and 4), with a mean therapeutic gain of 7.3 and 10.6 percentage points over weeks 1-4 and weeks 1-12, respectively. Headache was the most commonly reported adverse event (8.0% tegaserod versus 4.7% placebo). Diarrhoea was reported by 9.2% of patients on tegaserod (1.3% on placebo) and led to discontinuation in 2.8% of tegaserod patients. Conclusion: Tegaserod 6 mg b.i.d. is an effective, safe and well-tolerated treatment in patients suffering from IBS without diarrhoea as primary bowel symptom. [ABSTRACT FROM AUTHOR]

One-month intranasal toxicity studies were conducted with BMS-181885 at doses of 1.5, 9, or 15 mg/animal/day in rats and 4, 24, or 40 mg/animal/day in monkeys. A 1-month intermittent intranasal toxicity study was also conducted in monkeys at doses of 3, 6, and 12 mg/animal 3 days per week. BMS-181885 was generally well tolerated in rats but resulted in dose-dependent nasal mucosal injury, primarily characterized by subacute inflammation of the nasal mucosa, and degeneration, single-cell necrosis, and/or erosion of the olfactory epithelium and, to a lesser extent, the respiratory epithelium. In monkeys, daily BMS-181885 administration was well tolerated and produced similar dose-dependent nasal injury primarily characterized by subacute inflammation of the nasal mucosa with degeneration and erosion of the olfactory epithelium. In a separate experiment, intermittent administration also resulted in dose-dependent nasal injury. In cultured rat nasal mucosal cells, BMS-181885 was toxic to olfactory epithelial cells with a range of mean IC[sub 50] s between 44 and 291 muM. In contrast, BMS-181885 had no effect on respiratory epithelial cells up to its maximum solubility. Cytochrome P450 inhibition had no effect on the toxicity of BMS-181885 in olfactory epithelial cells but produced dose-dependent toxicity in respiratory epithelial cells, which was not present previously. The in vitro data suggest that parent drug, rather than a toxic metabolite, caused the drug-associated nasal mucosal injury. [ABSTRACT FROM AUTHOR]

Background: Aripiprazole is a new psychotropic agent that possesses a unique pharmacologic profile. The drug demonstrates mixed dopamine and serotonin agonist-antagonist activity and has been labeled a third-generation antipsychotic and dopamine-serotonin system stabilizer. Overdose experience is limited, especially in pediatrics. Case Series: Of five pediatric cases identified, toxicity was mainly evident in younger patients. A 2-year-old who ingested 40 mg experienced vomiting and significant lethargy lasting approximately 30 h. A 6-year-old who received two doses of aripiprazole therapeutically experienced lethargy, drooling, and flaccid facial muscles which improved with diphenhydramine. Two adolescents remained asymptomatic despite doses of 120 mg and 300 mg while a third adolescent with an unknown dose experienced transient lethargy. Conclusion: Aripiprazole is capable of producing marked lethargy and gastrointestinal upset in pediatric patients. Adolescents in this series experienced only minor, if any, clinical effects. Major clinical effects, i.e., seizures, dysrhythmias, were not reported in this series. [ABSTRACT FROM AUTHOR]

The article cites a research which explores whether serotonin agonists are putative antidepressants with a rapid onset of action, conducted by Guillame Lucas of McGill University and colleagues in Quebec. Researchers compared the drugs RS 67333 and prucalopride with a serotonin reuptake inhibitors (SSRI) in rats to test the antidepressant action of the two agonists. Findings revealed that the serotonin agonists worked much quicker and more effectively than conventional drugs.