5-HT3 antagonist 1

Chemotherapy-Induced Nausea and Vomiting: Pathogenesis, Recommendations, and New Trends

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.

Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting

Dietary and pharmacological treatment of abdominal pain in IBS

This review introduces the principles of visceral sensation and appraises the current approaches to management of visceral pain in functional GI diseases, principally IBS. These approaches include dietary measures including fibre supplementation, low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, and pharmacological approaches such as antispasmodics, peppermint oil, antidepressants (tricyclic agents, selective serotonin reuptake inhibitors), 5-HT₃ receptor antagonists (alosetron, ondansetron, ramosetron), non-absorbed antibiotic (rifaximin), secretagogues (lubiprostone, linaclotide), μ-opioid receptor (OR) and κ-OR agonist, δ-OR antagonist (eluxadoline), histamine H1 receptor antagonist (ebastine), neurokinin-2 receptor antagonist (ibodutant) and GABAergic agents (gabapentin and pregabalin). Efficacy and safety are discussed based on pivotal trials or published systematic reviews and meta-analysis, expressing ORs or relative risks and their 95% CIs. Potential new approaches may be based on recent insights on mucosal expression of genes, and microRNA and epigenetic markers in human biopsies and in animal models of visceral hypersensitivity.The objectives of this review are to appraise the physiology and anatomy of gut sensation and the efficacy in the relief of visceral pain (typically in IBS) of several classes of therapies. These include fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and different classes of medications (box 1). Box 1Classes of pharmacological agents for visceral painAntidepressants (tricyclic agents, selective serotonin reuptake inhibitors)Peppermint oil5-HT₃ receptor antagonists (alosetron, ondansetron, ramosetron)Non-absorbed antibiotic (rifaximin)Secretagogues (lubiprostone, linaclotide)μ-Opioid receptor (OR) and κ-OR agonist and δ-OR antagonist (eluxadoline)Histamine H1 receptor antagonist (ebastine)Neurokinin-2 receptor antagonist (ibodutant)GABAergic agents (gabapentin and pregabalin).

Granisetron, a selective 5-HT3 antagonist, reduces L-3,4-dihydroxyphenylalanine-induced abnormal involuntary movements in the 6-hydroxydopamine-lesioned rat

Administration of L-3,4-dihydroxyphenylalanine (L-DOPA) provides Parkinson's disease patients with effective symptomatic relief. However, long-term L-DOPA therapy is often marred by complications such as dyskinesia. We have previously demonstrated that serotonin type 3 (5-HT3) receptor blockade with the clinically available and highly selective antagonist ondansetron alleviates dyskinesia in the 6-hydroxydopamine (6-OHDA)-lesioned rat. Here, we sought to explore the antidyskinetic efficacy of granisetron, another clinically available 5-HT3 receptor antagonist. Rats were rendered hemi-parkinsonian by 6-OHDA injection in the medial forebrain bundle. Following induction of stable abnormal involuntary movements (AIMs), granisetron (0.0001, 0.001, 0.01, 0.1 and 1 mg/kg) or vehicle was acutely administered in combination with L-DOPA and the severity of AIMs, both duration and amplitude, was determined. We also assessed the effect of granisetron on L-DOPA antiparkinsonian action by performing the cylinder test. Adding granisetron (0.0001, 0.001, 0.01, 0.1 and 1 mg/kg) to L-DOPA resulted in a significant reduction of AIMs duration and amplitude, with certain parameters being reduced by as much as 38 and 45% (P < 0.05 and P < 0.001, respectively). The antidyskinetic effect of granisetron was not accompanied by a reduction of L-DOPA antiparkinsonian action. These results suggest that 5-HT3 blockade may reduce L-DOPA-induced dyskinesia without impairing the therapeutic efficacy of L-DOPA. However, a U-shaped dose-response curve obtained with certain parameters may limit the therapeutic potential of this strategy and require further investigation.

Combination of 5-HT3 Antagonist and Dexamethasone Is Superior to 5-HT3 Antagonist Alone for PONV Prophylaxis After Laparoscopic Surgeries: A Meta-analysis

Introduction: 5-Hydroxytryptamine type 3 (5-HT3) receptor antagonists are the most commonly used drugs for postoperative nausea vomiting (PONV) prophylaxis. Dexamethasone is another antiemetic with proven efficacy in reducing PONV. The aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the combination of dexamethasone and 5-HT3 antagonist versus a 5-HT3 antagonist alone as prophylaxis of PONV in laparoscopic surgical patients.
Methods: PubMed, PubMed Central, and CENTRAL databases were searched to identify those randomized trials that compared a 5-HT3 antagonist with the 5-HT3 antagonist and dexamethasone combination for PONV prophylaxis after laparoscopic surgeries.
Results: Data from 17 RCTs that evaluated 1402 patients were included. Results from our meta-analysis show that the combination of dexamethasone and a 5-HT3 receptor antagonist is more effective in preventing PONV than the 5-HT3 antagonist alone (odds ratio 0.38, 95% confidence interval [CI] 0.27-0.54; number needed to treat = 6.6), with no statistical heterogeneity (I = 0) among studies. The need for rescue antiemetic is also decreased in patients receiving the combination (odds ratio 0.21, 99% CI 0.10-0.46; number needed to treat = 6), although data are insufficient to detect any significant difference in incidence of adverse effects. In addition, patients in the combination group complained of less pain after 24 hours (Weighted Mean Difference -0.67, 99% CI -1.27 to -0.08).
Conclusion: Combination of a 5-HT3 receptor antagonist and dexamethasone is significantly more effective than 5-HT3 antagonist alone in preventing PONV after laparoscopic surgeries, with possible improvement in postoperative analgesia.