McMillan D E, Evans E B, Wessinger W D, Owens S M
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock.
J Pharmacol Exp Ther. 1988 Dec;247(3):1086-92.
The effects of a variety of arylcyclohexylamines, opioid drugs and other drugs were studied for phencyclidine-like effects in pigeons trained to discriminate phencyclidine (PCP) from saline. There was a good correlation between the relative potency of arylcyclohexylamines as PCP-like discriminative stimuli in pigeons and these drugs as discriminative stimuli in rats. Substitution of methyl groups on the piperidine or cyclohexyl rings of PCP reduced potency, but not efficacy, whereas substitution of hydroxyl groups decreased both potency and efficacy. Replacement of the phenyl ring with a thienyl ring increased PCP-like activity, but replacement of the piperidine ring with a pyrrolidine ring or a morpholine ring decreased potency. Compounds with methyl or ethyl groups on the nitrogen atom replacing the piperidine ring also were active. These data suggest that N-alkyl substitutions decrease potency but not efficacy, whereas hydroxylation of the cyclohexyl ring decreases efficacy as well. The data also support the suggestion that size of the aromatic ring is also a determinant of PCP-like activity. Both optical isomers of cyclazocine and N-allylnormetazocine were active as PCP-like discriminative stimuli, although the (-)-isomer was more potent than the (+)-isomer for cyclazocine and the reverse was true for N-allylnormetazocine. The pigeon shows less stereospecific activity with these drugs than the rat and especially the squirrel monkey. A variety of other opioid-like chemical structures, as well as other drugs such as d-amphetamine and pentobarbital, were inactive as PCP-like discriminative stimuli.
在经过训练能区分苯环利定（PCP）和生理盐水的鸽子身上，研究了多种芳基环己胺、阿片类药物及其他药物的苯环利定样效应。芳基环己胺作为鸽子体内苯环利定样辨别刺激物的相对效力，与这些药物作为大鼠体内辨别刺激物的效力之间存在良好的相关性。在PCP的哌啶环或环己基环上取代甲基会降低效力，但不会降低效能，而取代羟基则会同时降低效力和效能。用噻吩环取代苯环会增加苯环利定样活性，但用吡咯烷环或吗啉环取代哌啶环会降低效力。氮原子上带有甲基或乙基取代哌啶环的化合物也具有活性。这些数据表明，N-烷基取代会降低效力但不会降低效能，而环己基环的羟基化会同时降低效能。数据还支持这样的观点，即芳环的大小也是苯环利定样活性的一个决定因素。环唑辛和N-烯丙基去甲左啡诺的两种光学异构体作为苯环利定样辨别刺激物均具有活性，尽管对于环唑辛，（-）-异构体比（+）-异构体更有效，而对于N-烯丙基去甲左啡诺则相反。与大鼠尤其是松鼠猴相比，鸽子对这些药物的立体特异性活性较低。多种其他类阿片样化学结构以及其他药物如d-苯丙胺和戊巴比妥，作为苯环利定样辨别刺激物均无活性。
