NEUROCHEMICAL MECHANISM OF ACTION OF ANORECTIC DRUGS

Studies with dexfenfluramine, an anorectic agent which releases 5-hydr oxytryptamine (5-HT) from nerve terminals and inhibits its reuptake, h ave considerably increased our knowledge of the role of 5-HT in feedin g control. 5-HT1B receptors mediate the satiating effect of dexfenflur amine, whereas the mechanism by which 5-HT uptake inhibitors such as f luoxetine and sertraline cause anorexia is not clear. Anorexia induced by (+)-amphetamine, phentermine, diethylpropion and phenylpropanolami ne seems to be the result of their ability to increase the release of noradrenaline and/or dopamine from nerve terminals and inhibit their r euptake or, in the case of phenylpropanolamine, to stimulate directly alpha1-adrenoceptors. It has been suggested that beta- and alpha1-adre noceptors and D1 dopamine receptors are involved in their effect on fo od intake. The difficulties of extrapolation across species limit our knowledge of the mechanism of the anorectic action in humans. Signific ant advances in the treatment of feeding pathology will be linked to i dentifying new receptor types and subtypes for neurotransmitters and q uantifying and modelling eating disorders such as binge-eating and foo d craving.