Abstract
The multiplicity of serotonin (5-hydroxytryptamine; 5-HT) receptors far exceeds previous predictions. This overview attempts to answer the frequently asked question ‘Why are there so many serotonin receptor subtypes?’ The data indicate that although there has been a recent flurry of reports in the literature regarding the identification of ‘new’ serotonin receptor subtypes, the ‘primordial’ serotonin receptor evolved over 750 million years ago, a date likely to predate the evolution of muscarinic, dopaminergic and adrenergic receptor systems. This analysis also predicts that a significant number of both mammalian and invertebrate G protein-coupled serotonin receptor subtypes remain to be identified. The clinical significance of this multiplicity is only beginning to be appreciated. However, it is already evident that modulation of serotonin receptors can have important therapeutic benefits and the clinical usage of selective serotonin receptor subtype agents is very likely to increase significantly in the years ahead.
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