Fantegrossi William E, Murnane Kevin S, Reissig Chad J
Division of Neuroscience, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30322, USA.
Biochem Pharmacol. 2008 Jan 1;75(1):17-33. doi: 10.1016/j.bcp.2007.07.018. Epub 2007 Jul 20.
Until very recently, comparatively few scientists were studying hallucinogenic drugs. Nevertheless, selective antagonists are available for relevant serotonergic receptors, the majority of which have now been cloned, allowing for reasonably thorough pharmacological investigation. Animal models sensitive to the behavioral effects of the hallucinogens have been established and exploited. Sophisticated genetic techniques have enabled the development of mutant mice, which have proven useful in the study of hallucinogens. The capacity to study post-receptor signaling events has lead to the proposal of a plausible mechanism of action for these compounds. The tools currently available to study the hallucinogens are thus more plentiful and scientifically advanced than were those accessible to earlier researchers studying the opioids, benzodiazepines, cholinergics, or other centrally active compounds. The behavioral pharmacology of phenethylamine, tryptamine, and ergoline hallucinogens are described in this review, paying particular attention to important structure activity relationships which have emerged, receptors involved in their various actions, effects on conditioned and unconditioned behaviors, and in some cases, human psychopharmacology. As clinical interest in the therapeutic potential of these compounds is once again beginning to emerge, it is important to recognize the wealth of data derived from controlled preclinical studies on these compounds.
直到最近,研究致幻药物的科学家相对较少。然而,现在已有针对相关5-羟色胺能受体的选择性拮抗剂,其中大多数受体现已被克隆,这使得进行相当全面的药理学研究成为可能。对致幻剂行为效应敏感的动物模型已经建立并得到应用。先进的基因技术推动了突变小鼠的培育,事实证明这些小鼠在致幻剂研究中很有用。研究受体后信号转导事件的能力,促使人们提出了这些化合物可能的作用机制。因此,目前用于研究致幻剂的工具比早期研究阿片类药物、苯二氮䓬类药物、胆碱能药物或其他中枢活性化合物的研究人员所能获得的工具更加丰富,科学上也更先进。本文综述了苯乙胺、色胺和麦角灵致幻剂的行为药理学,特别关注已出现的重要构效关系、它们各种作用所涉及的受体、对条件性和非条件性行为的影响,以及在某些情况下的人体精神药理学。由于对这些化合物治疗潜力的临床兴趣再次开始显现,认识到从对这些化合物的对照临床前研究中获得的大量数据非常重要。