Failure of serotonin antagonist pizotifen to stimulate feeding or weight gain in free-feeding rats.
The serotonin antagonist pizotifen (BC-105) is prescribed as an appetite and weight enhancer (Mosegor--Wander, also commercialized under brand names Sanmigran or Sandomigran--Sandoz, Switzerland) for anorectic and convalescent humans. There has been, however, difficulty in demonstrating any orexigenic effect of pizotifen in laboratory animals. In the present report, the influence of chronic administration of pizotifen (0.1-30.0 mg/kg b.wt. per day, SC) on food intake and body weight gains was studied in rats given a standard diet (SD-energy content 14.5 kJ/g, 9% fibre), and in rats either habituated to a low energy content, carbohydrate-free diet (DD-7.3 kJ/g, 45% fibre), or given the DD after habituation to the SD. Pizotifen failed to increase food intake or weight gain. Nor did it shorten a period of initial depression of intake of the unfamiliar DD. On the contrary, pizotifen seemed to diminish food intake and weight gain in rats fed the low energy content diet. Since it has been reported that other 5-HT antagonists, e.g., cyproheptadine, methysergide, and ritanserin can enhance feeding, it is of some interest that pizotifen failed to affect food intake or weight gain in rats. The results suggest that the effects of pizotifen (and, possibly, of serotonin) in rats may differ from those in man. The possibility that feeding in the rat is mediated by 5-HT1 rather than 5-HT2 receptors is discussed.
Swiergiel
A H
AH
Institut de Pharmacologìe de l'Universite de Lausanne, Switzerland.
Peters
G
G
D000818:Animals; D001066:Appetite / Q000187:drug effects; D004032:Diet; D004327:Drinking Behavior / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D008297:Male; D010918:Pizotyline / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013876:Thiophenes / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects*
D013876:Thiophenes; D010918:Pizotyline