Glennon R A
Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0581, USA.
NIDA Res Monogr. 1991(116):25-44.
Animals trained to discriminate classical hallucinogens from saline have been used in the past decade to examine other hallucinogenic agents. Time course (onset, duration of action) and locus of action have been studied, SARs have been formulated, and mechanism of action has been investigated in detail. On the basis of DD studies in animals, it was proposed that hallucinogenic agents may produce their actions in humans via a 5-HT2 agonist mechanism and that certain phenalkylamine hallucinogens such as DOM and DOB might constitute the first known examples of 5-HT2 agonists. This led to the development of [3]HDOB and [125I]DOI for use in radioligand binding and autoradiographic studies and to the use of hallucinogen-trained animals as a functional behavioral model of 5-HT2 receptor activation. Animals trained to classical hallucinogens are more recently being used to evaluate novel designer drugs. It can be seen, then, that this paradigm, using hallucinogenic agents as training drugs, has proven to be quite useful for the investigation of hallucinogens and nonhallucinogens alike.
在过去十年中,经过训练能够区分经典致幻剂和生理盐水的动物被用于研究其他致幻剂。研究了时间进程(起效时间、作用持续时间)和作用位点,制定了构效关系,并且详细研究了作用机制。基于对动物的辨别性差异研究,有人提出致幻剂可能通过5-羟色胺2(5-HT2)激动剂机制在人类中产生作用,并且某些苯烷基胺类致幻剂,如2,5-二甲氧基-4-甲基苯丙胺(DOM)和2,5-二甲氧基-4-溴苯乙胺(DOB)可能是已知的首批5-HT2激动剂实例。这导致了用于放射性配体结合和放射自显影研究的[3H]DOB和[125I]DOI的开发,以及将经过致幻剂训练的动物用作5-HT2受体激活的功能性行为模型。最近,经过经典致幻剂训练的动物被用于评估新型设计药物。因此可以看出,这种以致幻剂作为训练药物的范式已被证明对研究致幻剂和非致幻剂都非常有用。