Serotonin 5-HT2A receptor agonist
drug class
A serotonin 5-HT2A receptor agonist, or simply 5-HT2A agonist, is a drug which acts as an agonist of the serotonin 5-HT2A receptor. The serotonin 5-HT2A receptor is one of 13 known human serotonin receptors. Serotonin 5-HT2A receptor agonists can be divided into two main groups: (1) serotonergic psychedelics such as LSD, psilocybin, and mescaline; and (2) non-hallucinogenic serotonin 5-HT2A receptor agonists such as lisuride, Ariadne, tabernanthalog, and zalsupindole, among others. Psychedelic and non-hallucinogenic serotonin 5-HT2A receptor agonists can be reliably distinguished from each other in scientific research using the head-twitch response assay in animals.
Agonists of the serotonin 5-HT2A receptor are generally not selective for this receptor and also interact with other serotonin receptors, such as the serotonin 5-HT1A, 5-HT2B, and/or 5-HT2C receptors, among others. However, highly selective serotonin 5-HT2A receptor agonists, such as TGF-8027, have also been developed. In addition to degree of selectivity for the serotonin 5-HT2A receptor, the serotonin 5-HT2A receptor activates a variety of different downstream signaling pathways, such as G protein and β-arrestin cascades, and serotonin 5-HT2A receptor agonists can have varying efficacies for activating these pathways, in turn resulting in different effects. Differing efficacies at different downstream signaling pathways relative to serotonin is also known as functional selectivity or biased agonism.
Serotonin 5-HT2A receptor agonists are frequently analogues of the neurotransmitter serotonin, and include tryptamines, phenethylamines, and ergolines and lysergamides, among other chemical classes.
In addition to the recreational and entheogenic use of serotonergic psychedelics, both psychedelic and non-hallucinogenic serotonin 5-HT2A receptor agonists, which act as psychoplastogens and have antidepressant-like effects in animals, may have applications in the treatment of psychiatric disorders such as depression, anxiety, and addiction.
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