Temporal differences in behavioral effect of fenfluramine and norfenfluramine.
Ten male rats were trained to discriminate the anorectic drug d,l-fenfluramine (2.0 mg/kg intraperitoneally administered) from its vehicle using a food-reinforced (fixed-ratio 10 schedule) two-lever operant task. Once learned, the fenfluramine stimulus was dose-dependent (ED50 = 0.8 mg/kg) and stereoselective with the d-isomer (ED50 = 0.6 mg/kg) approximate twice as potent as the l-isomer (ED50 = 1.2 mg/kg). Time-course data indicate that the fenfluramine metabolite norfenfluramine produces a significantly faster onset and longer duration of action than does the parent compound. The results suggest that both stereoisomers of fenfluramine have discriminative stimulus properties and that the fenfluramine metabolite, norfenfluramine, contributes to the discriminative stimulus properties of the parent drug.
Schechter
M D
MD
Department of Pharmacology, Northeastern Ohio Universities, College of Medicine, Rootstown 44272.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005277:Fenfluramine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D009642:Norfenfluramine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D009642:Norfenfluramine; D005277:Fenfluramine