The actions of fenfluramine and interaction with 5-HT3 receptor-antagonists to inhibit emesis in the ferret.
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 (1.0 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.
Costall
B
B
Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, UK.
Naylor
R J
RJ
Tattersall
F D
FD
D000818:Animals; D000932:Antiemetics; D002945:Cisplatin; D010134:Fenclonine / Q000494:pharmacology; D005277:Fenfluramine / Q000494:pharmacology*; D005289:Ferrets; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013237:Stereoisomerism; D000077526:Tropisetron; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
D000932:Antiemetics; D007211:Indoles; D012702:Serotonin Antagonists; D005277:Fenfluramine; D000077526:Tropisetron; D012110:Reserpine; D008787:Metoclopramide; D002945:Cisplatin; D010134:Fenclonine