The Actions of Fenfluramine and Interaction with 5-HT3 Receptor-Antagonists to Inhibit Emesis in the Ferret

Abstract

Abstract The racemate and (+)- and (-)-isomers of fenfluramine (5 mg kg−1 i.p., 1 h pretreatment) antagonized cisplatin-induced retching and vomiting in the ferret. The intravenous injection of (±)-fenfluramine administered on an established cisplatin-induced emesis antagonized the response within minutes of injection. The administration of a lower dose of (±)-fenfluramine (10 mg kg−1 i.p., 1 h pretreatment) failed to antagonize cisplatin-induced emesis when administered alone but enhanced the antiemetic effects of metoclopramide and ICS 205–930. This pretreatment with (±)-fenfluramine failed to enhance the antiemetic effects of zacopride. It is considered that an action of the racemate on presynaptic 5-HT/catecholaminergic systems to reduce neurotransmitter release may enhance the action of certain 5-HT3 receptor antagonists in controlling emesis induced by cisplatin.