Bolger G T, Rafferty M F, Weissman B A, Rice K C, Skolnick P
Pharmacol Biochem Behav. 1986 Jul;25(1):51-7. doi: 10.1016/0091-3057(86)90229-7.
Phencyclidine was previously shown to allosterically increase the apparent affinity of the dihydropyridine ( [3H]nitrendipine) calcium antagonist binding site in a lysed synaptosomal membrane preparation of rat forebrain. Treatment of a similar preparation of mouse forebrain with 4-isothiocyanato-1-(1-phenylcyclohexyl) piperidine (FOURPHIT), an acylating phencyclidine derivative, resulted in a concentration dependent (0.1-10 microM), irreversible, increase in the apparent affinity of [3H]nitrendipine in contrast to the effects of phencyclidine which were reversible. The FOURPHIT isomer, 1-[1-(3-isothiocyanatophenyl) cyclohexyl] piperidine (METAPHIT), (10 microM) also irreversibly increased the apparent affinity of [3H]nitrendipine, but was much less efficacious than FOURPHIT. Phencyclidine blocked the irreversible increase in the apparent affinity of [3H]nitrendipine produced by FOURPHIT. The interactions of multivalent cations and the calcium antagonist diltiazem with the [3H]nitrendipine binding site were altered following treatment of membranes with FOURPHIT. These studies suggest that FOURPHIT irreversibly interacts with the same sites as PCP, and thus may be a useful tool with which to further probe both the behavioral and biochemical interactions between phencyclidine and the dihydropyridine calcium antagonist binding site.
此前研究表明，在大鼠前脑裂解突触体膜制剂中，苯环己哌啶可别构增加二氢吡啶（[3H]尼群地平）钙拮抗剂结合位点的表观亲和力。用4-异硫氰酸-1-(1-苯基环己基)哌啶（FOURPHIT，一种酰化苯环己哌啶衍生物）处理小鼠前脑的类似制剂，结果显示[3H]尼群地平的表观亲和力呈浓度依赖性（0.1 - 10 microM）不可逆增加，这与苯环己哌啶的可逆性作用形成对比。FOURPHIT的异构体1-[1-(3-异硫氰酸苯基)环己基]哌啶（METAPHIT，10 microM）也不可逆地增加了[3H]尼群地平的表观亲和力，但效果远不如FOURPHIT。苯环己哌啶可阻断FOURPHIT引起的[3H]尼群地平表观亲和力的不可逆增加。在用FOURPHIT处理膜后，多价阳离子和钙拮抗剂地尔硫䓬与[3H]尼群地平结合位点的相互作用发生了改变。这些研究表明，FOURPHIT与苯环己哌啶作用于相同位点，因此可能是进一步探究苯环己哌啶与二氢吡啶钙拮抗剂结合位点之间行为和生化相互作用的有用工具。
