The molecular biology of serotonin receptors: Therapeutic implications for the interface of mood and psychosis

This review summarizes the molecular biology of serotonin (5-HT; 5-hydroxytryptamine) receptors and indicates the potential relevance of this information for the treatment of mood and psychotic disorders. At least 15 separate subtypes of 5-HT receptors have been identified by molecular clotting techniques to be distinct genetic entities. Subtle differences in the primary amino acid sequences of these receptors can yield large differences in ligand selectivity. Additionally: it Acts recently been discovered that drugs such as atypical antipsychotic drugs and serotonin-selective reuptake inhibitors may interact with a large number of heretofore unknown il 5-HT receptors . TThus clozapine, for distance, was high affinity for at least four separate 5-HT receptors, and it is unknown which of these receptors is essential for unique therapeutic efficacy. One way to approach these questions is to test subtype-selective agents, although there are few. of these currently available. Approaches to the design of subtype-selective ligands are described, including structure-based drugs design and combinational approaches. Modes of regulation of 5-HT receptors are also summarized, and it is emphasized that antipsychotic drugs and antidepressants likely exert their effects via nontranscriptional and posttranslational means. Understanding the cellular mechanisms by which 5-HT receptors are regulated by psychopharmacologic agents is likely to yield novel insights into drug action. (C) 1998 Society of Biological Psychiatry.