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.