d-Fenfluramine and salbutamol: two drugs causing anorexia through different neurochemical mechanisms.
Recent studies on some neurochemical and functional effects of d-fenfluramine and salbutamol in rats were summarized. It was found that d-fenfluramine releases serotonin almost exclusively from a reserpine-sensitive pool, but this is not the only mechanism by which it reduces food intake, as reserpine did not change its anorectic activity. The fact that d-norfenfluramine, the active metabolite of d-fenfluramine, uses mainly a reserpine-insensitive pool may help explain the failure of reserpine to reduce d-fenfluramine's effect on food intake. On the other hand, metergoline and chlorimipramine significantly reduced the effect of d-fenfluramine suggesting that drug's uptake into serotonin-confining neurons and serotonin release are important for the anorectic activity. The ability of d-fenfluramine to enhance serotonin function leads to a pattern of effects on various forms of eating that distinguishes this drug from d-amphetamine. In particular, studies with food-rewarded runway behaviour have clearly shown that d-fenfluramine reduces motivation for food whereas no such effect is clear for d-amphetamine. Salbutamol, a beta-adrenergic stimulant, was shown to reduce food intake in rats in a dose-dependent manner through a mechanism which seems to involve beta-adrenergic sites in the brain. The mechanism of action of salbutamol seems to be different from that of d-amphetamine since no cross-tolerance between the two drugs was found as regards their anorectic activity. Moreover, salbutamol and d-amphetamine affected differently some aspects of feeding behaviour in rats.
D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001067:Appetite Depressants; D002997:Clomipramine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects; D005277:Fenfluramine / Q000494:pharmacology*; D008711:Metergoline / Q000494:pharmacology; D009642:Norfenfluramine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D001067:Appetite Depressants; D012702:Serotonin Antagonists; D008711:Metergoline; D009642:Norfenfluramine; D005277:Fenfluramine; D012701:Serotonin; D002997:Clomipramine; D000420:Albuterol; D003913:Dextroamphetamine