Les bases de pharmacologie fondamentale du système sérotoninergique : application à la réponse antidépressive

Apr 27, 2016L'Encephale

How the serotonin system affects response to antidepressant drugs

AI simplified

Psychedelic Science on OpenScience ↗PubMed ↗DOI ↗

Abstract

Serotonin may be synthesized in the gut and central nervous system from the amino acid tryptophan.

Serotonin impacts various physiological functions beyond mood regulation.
It is synthesized by intestinal enterochromaffin cells and in the raphe nucleus of the CNS.
Around 15 serotonin receptors are involved, grouped into seven families, with most being G protein-coupled receptors.
SSRIs and other antidepressants indirectly increase serotonin levels, activating postsynaptic receptors rather than directly inhibiting the serotonin transporter.
Activation of specific serotonin receptors (5-HT1A, 5-HT1B, 5-HT1D, 5-HT2B, 5-HT4) is associated with antidepressant effects.
Blocking certain receptors (5-HT2A, 5-HT2C, 5-HT3, 5-HT6, 5-HT7) may also influence the effectiveness of antidepressants.

AI simplified

If serotonin (5-hydroxytryptamin [5-HT]) is well known for its role in mood regulation, it also impacts numerous physiological functions at periphery. Serotonin is synthetized at the periphery into the gut by intestinal enterochromaffin cells and in the central nervous system (CNS) in the raphe nucleus from the essential amino acid tryptophan. Physiological effects of 5-HT are mediated by about 15 serotoninergic receptors grouped into seven broad families (5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, 5-HT7 receptor families). Except 5-HT3 receptor, a ligand-gated ion channels, all the others are G protein-coupled receptors. Serotonin's homeostasis involves serotoninergic autoreceptor such as 5-HT1A, 5-HT1B, 5-HT1D, the enzymatic degradation of serotonin by monoamine oxidase A (MAO-A), and a transporter (serotoninergic transporter [SERT]). In the CNS, the SERT is a key target for various antidepressant drugs such as Selective Serotonin Reuptake Inhibitors (SSRI), Serotonin Norepinephrin Reuptake Inhibitors (SNRI) and tricyclics family. However, antidepressant activity of SERT inhibitors is not directly mediated by the SERT inhibition, but a consequence of postsynaptic 5-HT receptor activation following the increase in 5-HT levels in the synaptic cleft. In pharmacology, SSRIs are defined as indirect agonist of postsynaptic receptor. Among all the 5-HT receptors, 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2B and 5-HT4 receptors activation would mediate antidepressant effects. In the meanwhile, 5-HT2A, 5-HT2C, 5-HT3, 5-HT6 and 5-HT7 receptors activation would induce opposite effects. The best serotoninergic antidepressant would directly activate 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2B and 5-HT4 and would block 5-HT2A, 5-HT2C, 5-HT3, 5-HT6 and 5-HT7 receptor. If the chemical synthesis of such a compound may be compromised, SERT inhibition associated with the blockade of some but not all 5-HT receptor could shorten onset of action and/or improve antidepressant efficacy on the overall symptomatology of depression.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Les bases de pharmacologie fondamentale du système sérotoninergique : application à la réponse antidépressive

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the psychedelic science brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the psychedelic science brief