Anesthesia Pharmacology: Serotonin Pharmacology
Serotonin is a widely distributed indoleethylamine formed from L-tryptophan:
Serotonin synthesis may be inhibited by p-chlorophenylalanine (PCPA, fenclonine)
Following synthesis, Serotonin may be:
Rapidly inactivated by an oxidative step catalyzed by the enzyme, monoamine oxidase or MAO.
Furthermore, in the pineal gland, serotonin serves as a precursor for melatonin which is controlled in part by melanocyte-stimulating hormone.
Most serotonin (> 90%) is stored in enterochromaffin cells , localized in the GI tract.
Blood: platelets concentrate serotonin also and use a active carrier-mediated transport system which is similar to that found in nerve endings.
Raphe nuclei (brain stem)
In serotonergic neurons, neuronal cell bodies:
CNS serotonin involvement: include influences on:
Serotonin is degraded by the enzyme, monoamine oxidase, forming: 5-hydroxyindoleacetaldehyde.
5-hydroxyindoleacetaldehyde is then further oxidized in a reaction catalyzed by the enzyme aldehyde dehydrogenase.
The amount of 5-hydroxyindoleacetic acid (5-HIAA) excreted is a measure of serotonin synthesis.
Excessive serotonin synthesis may be helpful as a diagnostic test for certain tumors (e.g. carcinoid).
Serotonin Synthesis and Degradation: Summary
Burkhalter, A, Julius, D.J. and Katzung, B. Histamine, Serotonin and the Ergot Alkaloids (Section IV. Drugs with Important Actions on Smooth Muscle), in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 261-286.