A Comprehensive Pharmacological and Clinical Review of Serotonin (5-Hydroxytryptamine)

Executive Summary

Serotonin, or 5-hydroxytryptamine (5-HT), is a phylogenetically ancient and biologically ubiquitous monoamine that functions as a neurotransmitter, hormone, and paracrine signaling molecule. While colloquially known as the "happiness hormone" for its profound influence on mood and behavior within the central nervous system (CNS), its physiological roles extend far beyond the brain. The vast majority of the body's serotonin is synthesized and acts within the gastrointestinal tract, where it is a master regulator of motility, secretion, and sensation. This comprehensive review synthesizes the current scientific understanding of serotonin, beginning with its fundamental molecular identity and physicochemical properties. It traces the historical arc of its discovery, which presciently began in the gut and blood before its role in the brain was elucidated, mirroring the modern appreciation of the gut-brain axis.

The report details the complete life cycle of endogenous serotonin, from its biosynthesis from the essential amino acid L-tryptophan to its catabolism by monoamine oxidase. A central theme is the functional segregation of the central and peripheral serotonin pools by the blood-brain barrier, a division that presents significant challenges for systemic pharmacotherapy. The diverse and often paradoxical functions of serotonin—regulating everything from blood clotting and vascular tone to sleep, appetite, and sexual function—are explained through the lens of its complex receptor system. With at least 14 distinct receptor subtypes belonging to seven families, the physiological effect of serotonin is dictated not by the molecule itself, but by the specific receptor and signaling cascade activated in a given tissue.