Association of 5-HT3B Receptor Gene Polymorphisms with the Efficacy of Ondansetron for Postoperative Nausea and Vomiting

PURPOSE: Postoperative nausea and vomiting (PONV) is a common problem after general anesthesia. Although 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists have significantly reduced PONV, over 35% of patients treated with ondansetron can experience PONV. In this study, we investigated whether the Y129S and -100_-102AAG deletion polymorphisms of the 5-HT3B receptor gene affect the efficacy of ondansetron in preventing PONV. MATERIALS AND METHODS: Two hundred and forty-five adult patients who underwent laparoscopic cholecystectomy were enrolled. Ondansetron 0.1 mg/kg was intravenously administered 30 minutes before the end of surgery. Genomic DNA was prepared from blood samples using a nucleic acid isolation device. Both the Y129S variant and the -100_-102AAG deletion variant were screened for using a single base primer extension assay and a DNA direct sequencing method, respectively. The relationship between genetic polymorphisms and clinical outcomes of ondansetron treatment was investigated. RESULTS: Among the 5-HT3B AAG deletion genotypes, the incidence of PONV was higher in patients with the homomutant than with other genotypes during the first 2 hours after surgery (p=0.02). There were no significant differences in the incidence of PONV among genotypes at 2-24 hours after surgery. In the Y129S variants of the 5-HT3B receptor gene, there were no significant differences in the incidence of PONV among genotypes during the first 2 hours and at 2-24 hours after surgery. CONCLUSION: The response to ondansetron for PONV was significantly influenced by the -100_-102AAG deletion polymorphisms of the 5-HT3B gene. Thus, the -100_-102AAG deletion variants may be a pharmacogenetic predictor for responsiveness to ondansetron for PONV.

Involvement of opioid, adenosine and 5-HT3 receptors in antinociceptive effects of an ayurvedic polyherbal formulation

The present study was undertaken to evaluate the antinociceptive effects of an ayurvedic polyherbal formulation in rats and mice employing the tail immersion test and acetic acid-induced writhing test, respectively. With the tail immersion method, rats received two different doses [270 and 405 mg/kg BW, p.o.] of a formulation, pethidine [5.4 mg/kg BW, p.o.] as a reference standard and the combination of the higher dose of the formulation with naloxone [2 mg/kg, i.p.], an opioid receptor antagonist, and caffeine [16 mg/kg, i.p.], used as an adenosine receptor antagonist. In the acetic acid-induced writhing test, mice received two different doses [390 and 585 mg/kg, BW, p.o.] of formulation, diclofenac sodium [15 mg/kg, BW, p.o.] as a reference standard and the combination of the higher dose of the polyherbal formulation with ondansetron [0.5 mg/kg, i.p.], a serotonin receptor antagonist. The polyherbal formulation [405 mg/kg] exhibited a significant [p < 0.01] antinociceptive effect using the tail immersion method. In the acetic acid-induced writhing test, the formulation showed significant [p < 0.01] dose-dependent activity. The antinociceptive effect of the polyherbal formulation apparently involved an opiate-like mechanism, since its antinociceptive action was attenuated by naloxone pretreatment. In addition, antinociceptive activity was attenuated by caffeine and reversed by ondansetron pretreatment. Our data suggest that the polyherbal formulation possessed centrally and peripherally mediated antinociceptive properties. The activity could be mediated through opioid, adenosine, and serotonin receptors and via inhibition of cyclo-oxygenase- and/or lipoxygenase-dependent pathways