Serotonergic anorectics are correctly defined only if they enhance 5-HT transmission and have their anorectic effects inhibited by drugs that block 5-HT receptors. Fenfluramine, the prototype indirect 5-HT agonist, and its metabolite, norfenfluramine, act as 5-HT releasers and uptake inhibitors and are both more effective in the dextro form. They lack the stimulant activity and do not cause hyperthermia or stereotypical behaviour as is characteristic of amphetamines. The anorectic effect of those drugs is attenuated by metergoline, a 5-HT receptor antagonist, in animals and man; 5-HT uptake inhibitors such as fluoxetine, zimelidine, SL 810385, and sertraline also cause anorexia, but only sertraline antagonism by metergoline has been reported. The effect of serotonergic anorectics on 5-HT release has been poorly investigated. Quipazine and RU-24969 cause anorexia by acting directly on 5-HT post-synaptic receptors. Serotonergic nerve terminals take up [3H]-D-fenfluramine and bind with high affinity in rat brain; uptake, an active process, appears to occur at a different site than binding, which is not affected by ouabain or low temperature. Anorexia is probably induced by interaction with 5-HT1B receptors in the rat; the human equivalent of this receptor is not known, but the 5-HT1D type is a likely candidate.
|Number of pages||11|
|Journal||The British journal of psychiatry. Supplement|
|Publication status||Published - Dec 1989|
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