5-HT2A receptor

The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and functions as a G protein-coupled receptor (GPCR). It is a cell surface receptor that activates multiple intracellular signalling cascades.

Like all 5-HT2 receptors, the 5-HT2A receptor is coupled to the Gq/G11 signaling pathway. It is the primary excitatory receptor subtype among the serotonin-responsive GPCRs. The 5-HT2A receptor was initially noted for its central role as the primary target of serotonergic psychedelic drugs such as LSD and psilocybin mushrooms. It later regained research prominence when found to mediate, at least in part, the effects of many antipsychotic drugs, particularly atypical antipsychotics.

History

The serotonin receptors were split into two classes by John Gaddum and Picarelli in 1957 when it was discovered that some of the serotonin-induced changes in the gut could be blocked by morphine, while the remainder of the response was inhibited by dibenzyline (phenoxybenzamine), leading to the naming of M and D receptors, respectively. The 5-HT2A receptor is thought to correspond to what was originally described as D subtype of serotonin receptors by Gaddum and Picarelli.

In the era before molecular cloning, when radioligand binding and displacement was the only major tool, spiperone and LSD were shown to label two different 5-HT receptors, and neither of them displaced morphine, leading to naming of the 5-HT1, 5-HT2 and 5-HT3 receptors, corresponding to high affinity sites from LSD, spiperone and morphine, respectively. Later, it was shown that the 5-HT2 receptor was very close to the 5-HT1C receptor and they were thus were grouped together, renaming the 5-HT2 receptor into 5-HT2A receptor and the 5-HT1C receptor into the 5-HT2C receptor.