NEUROCHEMICAL MECHANISM OF ACTION OF ANORECTIC DRUGS

Studies with dexfenfluramine, an anorectic agent which releases 5-hydroxytryptamine (5-HT) from nerve terminals and inhibits its reuptake, have considerably increased our knowledge of the role of 5-HT in feeding control. 5-HT1B receptors mediate the satiating effect of dexfenfluramine, whereas the mechanism by which 5-HT uptake inhibitors such as fluoxetine and sertraline cause anorexia is not clear. Anorexia induced by (+)-amphetamine, phentermine, diethylpropion and phenylpropanolamine seems to be the result of their ability to increase the release of noradrenaline and/or dopamine from nerve terminals and inhibit their reuptake or, in the case of phenylpropanolamine, to stimulate directly alpha1-adrenoceptors. It has been suggested that beta- and alpha1-adrenoceptors and D1 dopamine receptors are involved in their effect on food intake. The difficulties of extrapolation across species limit our knowledge of the mechanism of the anorectic action in humans. Significant advances in the treatment of feeding pathology will be linked to identifying new receptor types and subtypes for neurotransmitters and quantifying and modelling eating disorders such as binge-eating and food craving.