Selective blockade of cytotoxic drug-induced emesis by 5-HT3 receptor antagonists in Suncus murinus.
Antiemetic effects of serotonin 5-HT3 receptor antagonists (ICS205-930, zacopride, BRL43694, GR38032F) were investigated in Suncus murinus. Veratrine, nicotine, copper sulfate, cisplatin, cyclophosphamide and motion sickness were used as emetic stimuli. Serotonin 5-HT3 receptor antagonists did not inhibit emetic responses to veratrine, nicotine, copper sulfate and motion sickness. However, cisplatin- and cyclophosphamide-induced emesis was strongly blocked by them. Both subcutaneous and intravenous injections of 5-HT3 antagonists were effective. Serotonin 5-HT1 and 5-HT2 receptor antagonists were less effective. These results clearly indicate that a 5-HT3 receptor-mediated mechanism(s) is involved in the emesis caused by cancer chemotherapeutic agents and that 5-HT3 receptor antagonists are very effective as prophylactic drugs.
Torii
Y
Y
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Saito
H
H
Matsuki
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007312:Eulipotyphla / Q000502:physiology*; D005260:Female; D008297:Male; D012702:Serotonin Antagonists; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000970:Antineoplastic Agents; D012702:Serotonin Antagonists