Isobolographic assessment of the effects of combinations of phenylpropanolamine and fenfluramine on food intake in rats.
Phenylpropanolamine (PPA) suppresses appetite in rats via activation of alpha 1-adrenergic receptors within the paraventricular hypothalamus (PVN). The serotonergic (5-HT) agonist fenfluramine (FEN) is thought to suppress appetite via stimulation of 5-HT release within the PVN rather than activation of adrenergic receptors. Whether a mixture of these neurochemically distinct anorexic drugs will serve as an effective appetite suppressant is unknown. In the present experiment, drug-drug interactions between PPA and FEN were explored using an isobologram technique. Fixed doses of PPA (0 vs. 5 mg/kg) were combined with various doses of FEN (1.25, 2.5, and 5.0 mg/kg) and fixed doses of FEN (0 vs. 2.5 mg/kg) were combined with various doses of PPA (0, 5, 10, and 15 mg/kg). Drug combinations were injected IP 30 min before a 1-h feeding trial in 16-h food-deprived rats. PPA and FEN were dose-additive in this paradigm, an outcome that supports the feasibility of a new appetite suppressant composed of a mixture of PPA and FEN.
Wellman
P J
PJ
Department of Psychology, Texas A&M University, College Station 77843-4235.
Tow
S
S
McMahon
L
L
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects*; D005277:Fenfluramine / Q000494:pharmacology*; D008297:Male; D010665:Phenylpropanolamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005277:Fenfluramine; D010665:Phenylpropanolamine