Fluphenazine, ICS 205-930 and dl-fenfluramine differentially antagonise drug-induced emesis in the ferret.
The intravenous injection of cisplatin (10 mg/kg), the subcutaneous injection of apomorphine (0.125-1 mg/kg) and lisuride (0.001-0.1 mg/kg), the oral administration of ipecacuanha (0.3-2.4 mg/kg) and the intragastric administration of copper sulphate (25-100 mg/kg), induced a vomiting and retching response in the ferret. Pretreatment with dl-fenfluramine (5 mg/kg i.p.) prevented or reduced the emesis induced by cisplatin, apomorphine, ipecacuanha and lisuride but failed to significantly antagonise copper sulphate-induced emesis. The 5-HT3 receptor antagonist ICS 205-930 (0.1 mg/kg i.p.) prevented emesis induced by cisplatin and ipecacuanha but failed to prevent or significantly reduce the emesis induced by apomorphine, lisuride or copper sulphate. Dopamine receptor antagonists, including fluphenazine (0.1-1.0 mg/kg i.p.) prevented apomorphine- and lisuride-induced emesis but were less potent or had inconsistent actions to antagonise cisplatin- or ipecacuanha-induced emesis and failed to inhibit the emesis induced by copper sulphate. The data indicate that dopamine and/or 5-HT3 receptor systems are involved in drug-induced emesis but that emesis caused by gastric irritation induced by copper sulphate is mediated by different receptor mechanisms.
Costall
B
B
Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, West Yorkshire, U.K.
Domeney
A M
AM
Naylor
R J
RJ
Owera-Atepo
J B
JB
Rudd
J A
JA
Tattersall
F D
FD
D000818:Animals; D001058:Apomorphine; D002945:Cisplatin; D003300:Copper; D019327:Copper Sulfate; D004639:Emetics / Q000037:antagonists & inhibitors*; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D005289:Ferrets; D005476:Fluphenazine / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007486:Ipecac; D008090:Lisuride; D008297:Male; D013237:Stereoisomerism; D000077526:Tropisetron; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D004639:Emetics; D007211:Indoles; D005277:Fenfluramine; D000077526:Tropisetron; D003300:Copper; D007486:Ipecac; D008090:Lisuride; D019327:Copper Sulfate; D001058:Apomorphine; D002945:Cisplatin; D005476:Fluphenazine