The serotonin 2A receptor is the most abundant excitatory serotonin receptor in the brain and the target for serotonergic psychedelics. Despite its importance, the mechanisms of action and structure−activity relationship of receptor agonists are not fully understood. Experimental 5-HT2AR structures have identified a hydrophobic tunnel lateral to the orthosteric site. Here, we have examined this...
Serotonergic psychedelics are described to have activation of the serotonin 2A receptor (5-HT2A) as their main pharmacological action. Despite their relevance, the molecular mechanisms underlying the psychedelic effects induced by certain 5-HT2A agonists remain elusive. One of the proposed hypotheses is the occurrence of biased agonism, defined as the preferential activation of certain...
The serotonin 2A receptor (5-HT2AR) is the mediator of the psychedelic effects of serotonergic psychedelics, which have shown promising results in clinical studies for several neuropsychiatric indications. The 5-HT2AR is able to signal through the Gαq and β-arrestin effector proteins, but it is currently not known how the different signaling pathways contribute to the therapeutic effects...