Receptors, Serotonin

Description

Serotonin is a major neurotransmitter in the brain and also is involved in a number of peripheral actions. Seven families or populations of 5-HT receptors have been identified (5-HT1–5-HT7), and several are divided into distinct subpopulations. Excluding splice variants, 14 different populations and subpopulations of 5-HT receptors have been cloned. Over the past 20 years, selective agonists and antagonists have been developed and identified for some of the subpopulations, but subpopulations remain for which selective agents have yet to be synthesized. The availability of such agents is important, because it aids functional investigations of the different 5-HT receptors. In addition to acting directly on 5-HT receptors, therapeutic agents with other mechanisms are available for influencing serotonergic transmission, including SSRIs and MAO inhibitors. Studies with 5-HT receptors have led to the introduction of agents useful for treating anxiety (e.g., buspirone), migraine (e.g., sumatriptan), IBS (e.g. tegaserod), and chemotherapy-induced emesis (e.g., ondansetron); numerous other agents are currently in clinical trials for the treatment of depression, schizophrenia, and obsessive-compulsive and other disorders. Investigations also have led to a greater understanding of cardiovascular pharmacology, obesity, neurodegenerative disorders, aggression, sexual behavior, and drug abuse, just to mention a few examples. Serotonin may even play an indirect role in techniques as diverse as acupuncture and transcendental meditation. To reiterate a phrase from the introduction, “ [I]t almost appears that serotonin is involved in everything”.
Seven families or populations of serotonergic receptors have been identified, 5-HT1 through 5-HT7, and several are divided into distinct subpopulations. The discovery of the individual populations and subpopulations of 5-HT receptors follows the approximate order of their numbering, and as a consequence, more is known about 5-HT1 and 5-HT2 receptors than about 5-HT6 and 5-HT7 receptors. Other factors contributing to our current lack of knowledge about certain receptor populations (i.e., 5-HT1E or 5-HT5 receptors) is the absence of agonists/antagonists with selectivity for these receptors.