EFFECTS OF A 5-HT1A RECEPTOR AGONIST ON ACUTE AND DELAYED CYCLOPHOSPHAMIDE-INDUCED VOMITING

LY228729 ,3,4,5-tetrahydrobenz-{c,d}indole-6-carboxamide}], agonist at the 5-HT1A subtype of 5-HT receptor, was studied as an antiemetic in pigeons dosed with a highly emetic oncolytic agent, cyclophosphamide. An intramuscular injection of 0.32 mg/kg of LY228729 administered 15 m in prior to the intravenous injection of 200 mg/kg of cyclophosphamide totally prevented the acute emetic response induced by cyclophosphami de. When used as a rescue therapy in a separate group of pigeons, LY22 8729 (0.32 mg/kg, i.m.) prevented further emetic episodes when it was administered after vomiting had already been induced by cyclophosphami de. Injections of LY228729 given at intervals over the next 2 d also a ttenuated the delayed emetic response induced by cyclophosphamide. LY2 28729 appears to be a broad spectrum antiemetic agent that is effectiv e against the anticipatory, the acute and the delayed stages of emesis induced by oncolytic agents. (C) 1997 Elsevier Science B.V.