The Serotonin Receptors From Molecular Pharmacology to Human Therapeutics

A comprehensive, state-of-the-art review of our current understanding of the molecular and structural biology of 5-HT receptors and their potential use for drug discovery. The authors describe the anatomical, cellular, and subcellular distribution of 5-HT receptors and demonstrate a powerful approach to elucidating their physiological role using knockout mice in which the 5-HT receptors were deleted. They also review our understanding of the physiological role(s) of 5-HT receptors based mainly on studies performed in genetically engineered mice. Highlights include discussions of the behavioral phenotypes of 5-HT receptor knockout animals, the molecular biology and pharmacology of 5-HT receptors, and insights into the complexity of 5-HT receptor signal transduction.

Molecular Biology and Genomic Organization of G Protein-Coupled Serotonin Receptors.- Structure and Function Reveal Insights in the Pharmacology of 5-HT Receptor Subtypes.- Polymorphic and Posttranscriptional Modifications of 5-HT Receptor Structure.- Strategies for the Development of Selective Serotonergic Agents.- 5-HT Receptor Signal Transduction Pathways.- Agonist-Directed Trafficking of 5-HT Receptor-Mediated Signal Transduction.- Identification of 5-HT2 and 5-HT4 Receptor-Interacting Proteins.- 5-HT Receptor-Associated Proteins (FRAPs).- Cellular and Subcellular Localization of Serotonin Receptors in the Central Nervous System.- Chemical Neuroanatomy of 5-HT Receptor Subtypes in the Mammalian Brain.- Modulation of the Neuronal Activity and Neurotransmitter Release by 5-HT1A and 5-HT1B/1D Receptors.- Electrophysiology of 5-HT2A Receptors and Relevance for Hallucinogen and Atypical Antipsychotic Drug Actions.- The Emergence of 5-HT2B Receptors as Targets to Avoid in Designing and Refining Pharmaceuticals.- The 5-HT3 Receptor.- 5-HT3 and 5-HT4 Receptors as Targets for Drug Discovery for Dementia.- Electrophysiological Properties of G?s-Coupled 5-HT Receptors (5-HT4, 5-HT6, 5-HT7).- 5-HT6 Receptors as Targets for the Treatment of Cognitive Deficits in Schizophrenia.- 5-HT7 Receptors as Favorable Pharmacological Targets for Drug Discovery.- Serotonin System Gene Knockouts.- Effects of Serotonin-Related Gene Deletion on Measures of Anxiety, Depression, and Neurotransmission.