FLUPHENAZINE, ICS 205-930 AND DL-FENFLURAMINE DIFFERENTIALLY ANTAGONIZE 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. © 1990.