Blockade of motion- and cisplatin-induced emesis by a 5-HT2 receptor agonist in Suncus murinus.
1. The effects of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOl), a 5-hydroxytryptamine 5-HT2A/5-HT2C receptor agonist, on motion- and cisplatin-induced emesis were studied in Suncus murinus. Subcutaneous injection of DOl, 30 min prior to the emetic stimuli, dose-dependently blocked the emesis induced by motion sickness and cisplatin (20 mg kg-1, i.p.) with estimated ID50 values of 640 and 780 micrograms kg-1, respectively. 2. alpha-Methyl-5-hydroxytryptamine (alpha-Me-5-HT), a peripheral 5-HT2A/5-HT2C receptor agonist, had no effect on motion- and cisplatin-induced emesis. 3. The antiemetic effects of DOl on motion- and cisplatin-induced emesis were attenuated by preadministration of ketanserin, a selective 5-HT2A receptor antagonist. 4. The present results suggest an inhibitory role for central 5-HT2 receptors in the emetic reflex mechanism and that a 5-HT2 receptor agonist may be a useful tool to investigate the involvement of 5-HT receptors in the emetic reflex.
Okada
F
F
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Saito
H
H
Matsuki
N
N
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D002945:Cisplatin; D008297:Male; D009041:Motion Sickness / Q000150:complications; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014418:Tupaiidae / Q000502:physiology*; D014839:Vomiting / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*
D000662:Amphetamines; D017366:Serotonin Receptor Agonists; C042390:alpha-methylserotonin; D012701:Serotonin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D002945:Cisplatin