Department of Chemistry, San Diego State University, San Diego, CA 92182, USA.
Oxid Med Cell Longev. 2009 Sep-Oct;2(4):181-90. doi: 10.4161/oxim.2.4.9380.
A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone counterpart. Electron transfer may play a role in electrical effects involving the nervous system in the brain. This approach is in accord with structure activity relationships involving mescaline, abused drugs, catecholamines, and etoposide. Inefficient demethylation is in keeping with the various drug properties, such as requirement for high dosage and slow acting. There is a discussion of receptor binding, electrical effects, cell signaling and other modes of action. Mescaline is a nonselective, seretonin receptor agonist. 5-HTP receptors are involved in the stimulus properties. Research addresses the aspect of stereochemical requirements. Receptor binding may involve the proposed quinone metabolite and/or the amino sidechain via protonation. Electroencephalographic studies were performed on the effects of mescaline on men. Spikes are elicited by stimulation of a cortical area. The potentials likely originate in nonsynaptic dendritic membranes. Receptor-mediated signaling pathways were examined which affect mescaline behavior. The hallucinogen belongs to the class of 2AR agonists which regulate pathways in cortical neurons. The research identifies neural and signaling mechanisms responsible for the biological effects. Recently, another hallucinogen, psilocybin, has been included within the unifying mechanistic framework. This mushroom constituent is hydrolyzed to the phenol psilocin, also active, which is subsequently oxidized to an ET o-quinone or iminoquinone.
先前曾从电子转移的角度提出过一种滥用药物的统一机制。三甲氧苯乙胺可以在基于儿茶酚代谢物与其醌对应物的氧化还原循环的理论框架内得到容纳。电子转移可能在涉及大脑神经系统的电效应中发挥作用。这种方法与涉及三甲氧苯乙胺、滥用药物、儿茶酚胺和依托泊苷的结构活性关系一致。低效去甲基化与各种药物特性一致，例如需要高剂量和缓慢作用。讨论了受体结合、电效应、细胞信号转导和其他作用模式。三甲氧苯乙胺是一种非选择性血清素受体激动剂。5-HTP 受体参与刺激特性。研究解决了立体化学要求的方面。受体结合可能涉及提议的醌代谢物和/或通过质子化的氨基酸侧链。对男性进行了电脑电图研究，以研究三甲氧苯乙胺对其的影响。通过刺激皮质区域引发尖峰。这些电势可能源自非突触树突膜。检查了影响三甲氧苯乙胺行为的受体介导的信号通路。致幻剂属于 2AR 激动剂类别，可调节皮质神经元中的途径。该研究确定了负责生物学效应的神经和信号机制。最近，另一种致幻剂，裸盖菇素，已被纳入统一的机制框架中。这种蘑菇成分被水解为具有活性的酚基裸盖菇素，随后被氧化为 ET o-醌或亚氨基醌。
