Gumpper Ryan H, Nichols David E
Department of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Br J Pharmacol. 2024 Oct 2. doi: 10.1111/bph.17361.
This brief review highlights some of the structure-activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines and certain tryptamines, which possess psychedelic activity in humans. Where they are known, we point out the underlying molecular mechanisms utilized by each of the three chemotypes of psychedelic molecules. With a focus on the 5-HT receptor subtype, a G-protein coupled receptor known to be the primary target of psychedelics, we refer to several X-ray and cryoEM structures, with a variety of ligands bound, to illustrate the underlying atomistic basis for some of the known pharmacological observations of psychedelic drug actions.
本简要综述重点介绍了经典血清素能致幻剂的一些构效关系。特别是，我们讨论了三种化学类型的结构特征：苯乙胺类、麦角灵类和某些色胺类，它们在人类中具有致幻活性。在已知的情况下，我们指出了这三种致幻分子化学类型各自所利用的潜在分子机制。以5-HT受体亚型为重点，这是一种已知为致幻剂主要靶点的G蛋白偶联受体，我们引用了几种结合了各种配体的X射线和冷冻电镜结构，以说明致幻药物作用的一些已知药理学观察结果的潜在原子基础。
