Department of Zoology, University of Oklahoma, Norman, Oklahoma, United States of America.
PLoS One. 2010 Feb 2;5(2):e9019. doi: 10.1371/journal.pone.0009019.
We currently understand the mental effects of psychedelics to be caused by agonism or partial agonism of 5-HT(2A) (and possibly 5-HT(2C)) receptors, and we understand that psychedelic drugs, especially phenylalkylamines, are fairly selective for these two receptors. This manuscript is a reference work on the receptor affinity pharmacology of psychedelic drugs. New data is presented on the affinity of twenty-five psychedelic drugs at fifty-one receptors, transporters, and ion channels, assayed by the National Institute of Mental Health-Psychoactive Drug Screening Program (NIMH-PDSP). In addition, comparable data gathered from the literature on ten additional drugs is also presented (mostly assayed by the NIMH-PDSP). A new method is introduced for normalizing affinity (K(i)) data that factors out potency so that the multi-receptor affinity profiles of different drugs can be directly compared and contrasted. The method is then used to compare the thirty-five drugs in graphical and tabular form. It is shown that psychedelic drugs, especially phenylalkylamines, are not as selective as generally believed, interacting with forty-two of forty-nine broadly assayed sites. The thirty-five drugs of the study have very diverse patterns of interaction with different classes of receptors, emphasizing eighteen different receptors. This diversity of receptor interaction may underlie the qualitative diversity of these drugs. It should be possible to use this diverse set of drugs as probes into the roles played by the various receptor systems in the human mind.
我们目前认为迷幻剂的心理效应是由 5-HT（2A）（可能还有 5-HT（2C））受体的激动或部分激动引起的，并且我们知道迷幻药物，尤其是苯乙胺类药物，对这两种受体具有相当的选择性。本文是一本关于迷幻药物受体亲和力药理学的参考著作。新数据显示，二十五种迷幻药物在五十一个受体、转运体和离子通道上的亲和力，由美国国立精神卫生研究所-精神药物筛选计划（NIMH-PDSP）测定。此外，还介绍了从文献中收集的另外十种药物的可比数据（主要由 NIMH-PDSP 测定）。引入了一种新的方法来归一化亲和力（K(i)）数据，该方法消除了效力因素，以便可以直接比较和对比不同药物的多受体亲和力谱。然后使用该方法以图形和表格形式比较了三十五种药物。结果表明，迷幻药物，尤其是苯乙胺类药物，并不像普遍认为的那样具有选择性，与广泛测定的四十九个位点中的四十个位点相互作用。本研究中的三十五种药物与不同类别的受体有非常不同的相互作用模式，强调了十八种不同的受体。这种受体相互作用的多样性可能是这些药物定性多样性的基础。应该可以使用这一组多样化的药物作为研究人类大脑中各种受体系统所起作用的探针。
