5-HT1A and beyond: the role of serotonin and its receptors in depression and the antidepressant response.

Since its discovery 50 years ago, the role of the indoleamine 5-HT (5-hydroxytryptamine; serotonin) in the pathogenesis of depression and in the mechanism of action of antidepressant drugs has been the subject of considerable research. Advances in molecular biology and radioligand techniques have led to the functional characterisation of at least 14 serotonin receptor subtypes. This classification has led to the development of selective compounds that have aided in the efforts of dissecting the complex role of 5-HT in depression and in mediating the antidepressant response. This review focuses largely on novel strategies of targeting specific 5-HT receptors subtypes, especially the presynaptic 5-HT(1A) and 5-HT(1B/1D) receptors. These subtypes are of primary importance in that they control the firing of the 5-HT neuron and the release of 5-HT. In addition, a number of postsynaptic 5-HT receptors have been shown to be dysfunctional in depression and are also potential targets for a number of antidepressants. We conclude that selective targeting of 5-HT receptors may lead to a faster acting and more efficient antidepressant response. Copyright 2000 John Wiley & Sons, Ltd.