Structure–activity relationships of serotonin 5‐HT2Aagonists

Summary

Of the 14 known serotonin receptor types, the 5-HT2A receptor is one of the most studied. In the brain, it regulates cortical function and cognition, is the main target for hallucinogenic drugs like LSD, and is also a target for newer atypical antipsychotic drugs that act as antagonists or inverse agonists. Three chemical classes of agonists exist: tryptamines, ergolines, and phenethylamines. Key structural features for agonist activity are identified, and some agonists share common features. Much of the structure-activity relationship knowledge comes from human studies conducted before modern pharmacological techniques.

Study at a glance

Abstract

Abstract Of the 14 known types of serotonin receptors one of the most extensively studied is the 5‐HT 2A (5‐hydroxytryptamine) receptor. In the brain, this receptor plays a key role in regulation of cortical function and cognition, appears to be the principal target for the hallucinogenic/psychedelic drugs such as lysergic acid diethylamide (LSD), and also is a target for the newest atypical antipsychotic agents, which are antagonists or inverse agonists at this site. Among the structure–activity relationships that are known for this receptor type, there are three chemical classes of agonists: tryptamines, ergolines, and phenethylamines. Important structural features are identified for agonist activity and some of these agonists have features in common. In addition to effects at the receptor will be the focus, these drugs are also hallucinogenic (psychedelic) agents, and much of the SAR was developed on the basis of effects in humans, before modern pharmacological techniques were available. A certain amount of our knowledge therefore relies on those human studies. WIREs Membr Transp Signal 2012, 1:559–579. doi: 10.1002/wmts.42 For further resources related to this article, please visit the WIREs website .