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Serotonin (5-hydroxytryptamine; 5-HT) is present in highest concentration in blood platelets and in the gastrointestinal tract. Lesser amounts are found in the brain and in the retina.


Synthesis & Metabolism

Serotonin is formed in the body by hydroxylation and decarboxylation of the essential amino acid tryptophan. The first step is catalyzed by tryptophan hydroxylase while the second step is catalyzed by 5-Hydroxytryptophan decarboxylase.

After release from neurons, most of the released serotonin is recaptured by active reuptake and inactivated by MAO.

In the pineal gland, serotonin is converted to melatonin.

Reserpine can deplete stored serotonin.


The number of cloned and characterized serotonin receptors is increasing rapidly. Currently, there are seven clones receptors (5-HT1 to 5-HT7). The 5-HT1 group has 5 subtypes, the 5-HT2­ group has 3 subtypes and 5-HT5 group has 2 subtypes.

Most of the receptors are coupled to G-proteins and affect adenylyl cyclase or phospholipase C. 5-HT3 receptors, on the other hand, are ionotropic.

Role in the brain

Most serotonin pathways originate from neurons in the raphe or midline regions of the pons and upper brain stem. Serotonin-containing neurons are unmyelinated and diffusely project throughout most of the CNS.

In most areas of the CNS, 5-HT has a strong inhibitory action. This action is mediated by 5-HT1A receptors and is associated with membrane hyperpolarization caused by an increase in potassium conductance. Some cell types are slowly excited by 5-HT owing to its blockade of potassium channels via 5-HT2 or 5-HT4 receptors.

Other proposed regulatory functions of 5-HT-containing neurons include sleep, temperature, appetite, and neuroendocrine control.


  1. Ganong WF. Review of medical physiology. 22nd ed. New York: Lange Medical Books/McGraw-Hill; 2005.
  2. Katzung BG. Basic & clinical pharmacology. 10th ed. New York: McGraw-Hill Medical; 2007.
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