Nichols David E
Division of Chemical Biology and Medicinal Chemistry, University of North Carolina, Chapel Hill, NC, 27514, USA.
Curr Top Behav Neurosci. 2018;36:1-43. doi: 10.1007/7854_2017_475.
This chapter will summarize structure-activity relationships (SAR) that are known for the classic serotonergic hallucinogens (aka psychedelics), focusing on the three chemical types: tryptamines, ergolines, and phenethylamines. In the brain, the serotonin 5-HT receptor plays a key role in regulation of cortical function and cognition, and also appears to be the principal target for hallucinogenic/psychedelic drugs such as LSD. It is one of the most extensively studied of the 14 known types of serotonin receptors. Important structural features will be identified for activity and, where possible, those that the psychedelics have in common will be discussed. Because activation of the 5-HT receptor is the principal mechanism of action for psychedelics, compounds with 5-HT agonist activity generally are quickly discarded by the pharmaceutical industry. Thus, most of the research on psychedelics can be related to activation of 5-HT receptors. Therefore, much of the discussion will include not only clinical or anecdotal studies, but also will consider data from animal models as well as a certain amount of molecular pharmacology where it is known.
本章将总结经典血清素能致幻剂（又称迷幻剂）的构效关系（SAR），重点关注三种化学类型：色胺类、麦角灵类和苯乙胺类。在大脑中，血清素5-HT受体在调节皮层功能和认知方面起着关键作用，并且似乎也是诸如麦角酸二乙酰胺（LSD）等致幻/迷幻药物的主要靶点。它是已知的14种血清素受体类型中研究最为广泛的一种。将确定对活性重要的结构特征，并在可能的情况下讨论迷幻剂共有的那些特征。由于5-HT受体的激活是迷幻剂的主要作用机制，具有5-HT激动剂活性的化合物通常会被制药行业迅速淘汰。因此，大多数关于迷幻剂的研究都与5-HT受体的激活有关。所以，大部分讨论不仅将包括临床或轶事研究，还将考虑来自动物模型的数据以及已知的一定量分子药理学数据。
