Bolger G T, Rafferty M F, Skolnick P
Pharmacol Biochem Behav. 1986 Mar;24(3):417-23. doi: 10.1016/0091-3057(86)90534-4.
The abilities of compounds structurally or pharmacologically related to phencyclidine to increase the apparent affinity of the [3H]dihydropyridine calcium channel antagonist [3H]nitrendipine were examined in lysed synaptosomal membrane preparations of rat brain. The p-bromo analog of phencyclidine (1-(1-(4-bromophenyl)cyclohexyl)piperidine) was the most efficacious compound tested in enhancing the apparent affinity of [3H]nitrendipine. The efficacy of this compound was approximately two-fold greater than PCP. The stereoisomers of PCMP (1-(1-phenylcyclohexyl-3-methylpiperidine) were also more efficacious than phencyclidine, although only a small degree of stereoselectivity was observed. Levoxadrol, dexoxadrol and the enantiomers of ketamine did not potentiate [3H]nitrendipine binding. The enantiomers of SKF 10047 (n-allylormetazocine), dextrorphan, levorphanol and the ion channel toxins histrionicotoxin and pumiliotoxin-B also increased the apparent affinity of [3H]nitrendipine, while several local anesthetics and mu-opiate receptor ligands were without effect. These studies suggest that the ability of phencyclidine and structurally related compounds to increase the apparent affinity of [3H]nitrendipine is not mediated through an interaction with phencyclidine receptors, but may represent a unique site for allosteric modulation of neuronal dihydropyridine calcium channel antagonist binding sites.
在大鼠脑裂解突触体膜制剂中，研究了与苯环己哌啶结构或药理相关的化合物增加[3H]二氢吡啶钙通道拮抗剂[3H]尼群地平表观亲和力的能力。苯环己哌啶的对溴类似物（1-(1-(4-溴苯基)环己基)哌啶）是测试的增强[3H]尼群地平表观亲和力最有效的化合物。该化合物的效力比苯环己哌啶大约高两倍。PCMP（1-(1-苯基环己基-3-甲基哌啶)）的立体异构体也比苯环己哌啶更有效，尽管仅观察到较小程度的立体选择性。左吗喃、右吗喃和氯胺酮的对映体不能增强[3H]尼群地平的结合。SKF 10047（烯丙基去甲唑啉）的对映体、右啡烷、左啡诺以及离子通道毒素组胺毒素和箭毒蛙毒素-B也增加了[3H]尼群地平的表观亲和力，而几种局部麻醉剂和μ-阿片受体配体则无此作用。这些研究表明，苯环己哌啶和结构相关化合物增加[3H]尼群地平表观亲和力的能力不是通过与苯环己哌啶受体相互作用介导的，而是可能代表神经元二氢吡啶钙通道拮抗剂结合位点变构调节的一个独特位点。
