Effects of a 5-HT1A receptor agonist on acute and delayed cyclophosphamide-induced vomiting.
LY228729 [(-)-4(dipropylamino)-1,3,4,5-tetrahydrobenz-[c,d]indole-6-carboxa mide]], an 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 min prior to the intravenous injection of 200 mg/kg of cyclophosphamide totally prevented the acute emetic response induced by cyclophosphamide. When used as a rescue therapy in a separate group of pigeons, LY228729 (0.32 mg/kg, i.m.) prevented further emetic episodes when it was administered after vomiting had already been induced by cyclophosphamide. Injections of LY228729 given at intervals over the next 2 d also attenuated the delayed emetic response induced by cyclophosphamide. LY228729 appears to be a broad spectrum antiemetic agent that is effective against the anticipatory, the acute and the delayed stages of emesis induced by oncolytic agents.
Wolff
M C
MC
Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, IN 46285, USA.
Leander
J D
JD
D000818:Animals; D018906:Antineoplastic Agents, Alkylating; D010856:Columbidae; D003520:Cyclophosphamide; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D018906:Antineoplastic Agents, Alkylating; D004873:Ergolines; D017366:Serotonin Receptor Agonists; C066421:LY 178210; D003520:Cyclophosphamide