Gabapentsal ameliorate cisplatin-induced vomiting in pigeons: neurochemical evidences and the involvement of serotonin and dopamine modulation.

Cisplatin is used for treatment of various carcinomas in clinics but is associated with the adverse effects of nausea and vomiting. We investigated the antiemetic effect of gabapentsal; a gabapentinoid derivative against cisplatin (10 mg/kg) induced vomiting in pigeons and the neurochemical mechanisms centrally and peripherally and the involvement of dopaminergic receptors. Established video recording setup was used for behavioral experiments while High Performance Liquid Chromatography system coupled with electrochemical detector (HPLC-ECD) was used for the quantification of neurotransmitters 5-hydroxytryptamine (5HT) and its metabolite; 5-hydroxy indole acetic acid (5-HIAA), dopamine (DA) and its metabolites; dihydroxy phenyl acetic acid (DOPAC), homovanillic acid (HVA) and noradrenaline (NA) centrally in brain stem while, peripherally in small intestine. Cisplatin (10 mg/kg i.v.) induced emesis without lethality up to the observation period (3 h.). Gabapentsal attenuated cisplatin induced emesis ~ 77.22%; the standard drug, gabapentin (GB; 100 mg/kg), produced ~ 57.55% reduction. Gabapentsal suppressed (p < 0.05 - p < 0.01) the concentration of 5HT and 5-HIAA in the brain stem and intestine. In continuation, a decline (P < 0.05 - p < 0.01) in the concentration of DA and its metabolite DOPAC in the brain stem while DA concentration was decreased (p < 0.05) in the intestine only. The standard gabapentin (100 mg/kg) decreased (p < 0.05) the concentration of 5HT and NA in the intestine only. Furthermore; gabapentsal attenuated (p < 0.001) quinpirole (3 mg/kg) induced vomiting but no effect on neurotransmitters and their metabolites was noted. In conclusion, gabapentsal has antiemetic activity against cisplatin and quinpirole induced vomiting mediated by serotonergic and dopaminergic components centrally and peripherally.