Gastromotor mechanism of fenfluramine anorexia.
A gastric slowing effect of fenfluramine accounts for most of the drug's suppressant effect on food intake in freely feeding rats. It is conceivable on the evidence to date that this gastromotor action of fenfluramine explains all its effects on appetite and metabolism, but additional peripheral and central effects--such as motor inhibition--are likely. Rate of gastric emptying is quantitatively the dominant physiological control of appetite: it determines the duration for which absorption of a meal sustains metabolic satiety; it also influences gastric distension, which can be a source of innate satiation and of learned carbohydrate-specific satiation. Since most of the neurotransmitter serotonin (5HT) resides in the gastrointestinal wall, not the brain, gastromotor suppression of appetite should be the first working hypothesis for a serotoninergic drug such as fenfluramine. The largest effect on food intake that arises from gastric slowing by fenfluramine and active metabolites is a lengthening of the period of satiety after a meal of a given size. The residue of this extended satiety could reduce appetite at a subsequent fixed mealtime and hence the size of such a meal. Fenfluramine appears not to intensify satiation processes generated by a meal. Rather, it affects eating processes from the start. Also, fenfluramine disrupts learned carbohydrate-specific satiation operative within a meal. This negates the claim that fenfluramine reduces carbohydrate-specific appetite--which in any case (like other claims that drugs modulate nutrient selection) is not based on adequately designed dietary selection tests.
D000818:Animals; D004040:Dietary Carbohydrates; D004044:Dietary Proteins; D005247:Feeding Behavior / Q000187:drug effects*; D005277:Fenfluramine / Q000494:pharmacology*; D005518:Food Preferences / Q000187:drug effects; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D051381:Rats; D012527:Satiation / Q000187:drug effects
D004040:Dietary Carbohydrates; D004044:Dietary Proteins; D005277:Fenfluramine