COMPARISON OF THE ANTIEMETIC EFFECTS OF A 5-HT1A AGONIST, LY228729, AND 5-HT3 ANTAGONISTS IN THE PIGEON

Vomiting may be induced by a variety of agents such as drugs, oncolyti cs, and provocative motion, as well as being conditioned to occur to e nvironmental stimuli. Such emesis has recently been shown to be blocke d by agonists at the 5-HT1A subtype of serotonin receptor. The antieme tic effects of LY228729 1,3,4,5-tetrahydrobenz-(c,d)indole-6-carboxami de], a 5-HT1A receptor agonist, were tested and compared to the antiem etic effects of the 5-HT3 receptor antagonists ondansetron, tropisetro n, and MDL 72222 (3-tropanyl-3,5-dichlorobenzoate). The emetic stimuli tested are known to be blocked by 5-HT3 antagonists in species other than the pigeon. In the pigeon, LY228729 totally abolished vomiting in duced by fully emetic doses of cisplatin (10 mg/kg), ipecac (3 ml/kg), emetine (10 mg/kg), and a 5-HT3 agonist, m-(chlorophenyl)-biguanide ( 1.25 mg/kg). MDL 72222 blocked ipecac-induced vomiting in a dose-relat ed manner and was partially effective in attenuating cisplatin-induced emesis. Ondansetron and tropisetron were partially effective in block ing emetine- and mCPBG-induced vomiting. Ondansetron exhibited an intr insic emetic response that could not be blocked by MDL 72222, but whic h was eliminated by LY228729. It was concluded that 5-HT1A agonists ar e more effective in the pigeon than are 5-HT3 antagonists against thes e types of emetic stimuli. These results broaden the range of emetic s timuli that are blocked by 5-HT1A agonists in the pigeon.