Serotonin

(BAN)
Synonyms: Enteramina; Enteramine; 5-Hidroxitriptamina; 5-HT; 5-Hydroxytryptamine; Serotonina. 3-(2-Aminoethyl)-1H-indol-5-ol.
Cyrillic synonym: Серотонин.

Chemical information

Chemical formula: C10H12N2O = 176.2.
CAS — 50-67-9.

Profile

Serotonin, which is synthesised in the body from the essential amino acid tryptophan, is found in the brain, blood platelets, and throughout the gastrointestinal tract. It acts as a biochemical mediator and its roles include involvement in CNS neurotransmission, haemostasis, vascular spasm, and gastrointestinal motility. Abnormalities within the serotonin system are associated with a variety of disorders and many drugs have been developed to manipulate serotonin concentrations. Serotonin itself may be of value in the treatment of posthypoxic myoclonus. Concentrations of endogenous serotonin may be increased through synthesis and serotonin precursors have been given for the treatment of depression. Some antidepressants increase serotonin concentrations by inhibiting the metabolism of monoamine oxidase type A, the enzyme that deaminates serotonin. Examples include the older non-selective irreversible inhibitors of monoamine oxidase types A and B (MAOIs) such as phenelzine, and the newer selective reversible inhibitors of monoamine oxidase type A (RIMAs) such as moclobemide. Drugs that inhibit the neuronal reuptake of serotonin after release (and thus potentiate its action) are also used in the treatment of depression. They include tricyclic antidepressants such as amitriptyline, the selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, and selective serotonin and noradrenaline reuptake inhibitors (SNRIs) such as venlafaxine. Some SSRIs and SNRIs are also used in the management of anxiety disorders, and SSRIs have been tried in the management of premature ejaculation. Sibutramine is an SNRI used in the management of obesity. Serotonin receptors, a major site of drug action, are classified by structure and function into seven families: 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 with each family having further subtypes. Consequently, drugs acting on serotonin receptors exhibit widely differing chemical structures and diverse pharmacological activities depending on which receptor subtype they act on and whether they act as agonists or antagonists. Serotonin receptor activity is complex and it is possible for the same disorder to be treated by both serotonin agonists or antagonists. For example, serotonin antagonists used in the treatment of migraine include the older ergot-derived compounds such as methysergide and metergoline whereas the newer triptans such as sumatriptan are selective 5-HT1 agonists. Buspirone is a 5-HT1A partial agonist used in the treatment of anxiety disorders. Cisapride is a 5-HT4 agonist used for gastrointestinal disorders. 5-HT2C agonists are under investigation for obesity. Many different drugs act as serotonin antagonists. They include sedating antihistamines such as carbinoxamine, cyproheptadine, methdilazine, and promethazine used for allergic conditions. Some antiserotonergic antihistamines such as cyproheptadine, oxetorone, and pizotifen are also used in the management of migraine. Antagonists specific for the 5-HT2A/2C receptor include the antihypertensive ketanserin, the antipsychotic risperidone, and the antidepressant trazodone. The antipsychotic clozapine also has antiserotonergic activity at the 5-HT2A/2C receptor in addition to its other properties. Ondansetron is a 5-HT3 antagonist used for chemotherapyinduced emesis and postoperative nausea and vomiting. Drugs with other mechanisms of action involving serotonin systems include fenclonine, an inhibitor of serotonin synthesis that has been used in the treatment of carcinoid syndrome. Reserpine depletes serotonin stores in the brain, heart, and many other organs and has been used in hypertension and psychoses. Fenfluramine and its isomer dexfenfluramine appear to stimulate the release of serotonin and selectively inhibit its reuptake resulting in increased CNS serotonin concentrations; both were formerly used in the treatment of obesity. Some hallucinogenic drugs of abuse such as bufotenine and lysergide have serotonergic properties. Serotonin also occurs in stinging nettles (Urtica dioica), bananas, and other fruit, and in the stings of wasps and scorpions.
1. Hindle AT. Recent developments in the physiology and pharmacology of 5-hydroxytryptamine. Br J Anaesth 1994; 73: 395–407
2. Hoyer D, et al. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 1994; 46: 157–203.
Published May 08, 2019.