Altura B T, Quirion R, Pert C B, Altura B M
Proc Natl Acad Sci U S A. 1983 Feb;80(3):865-9. doi: 10.1073/pnas.80.3.865.
Several psychotomimetic phencyclidine (PCP) analogs--N-ethyl-l-phenylcyclohexylamine (PCE), N-[1-(2-thienyl)cyclohexyl]piperidine (TCP), N-[1-(thienyl)cyclohexyl ))pyrrolidine (THP), ketamine, and N,N-dimethyl-l-phenyl-cyclohexylamine (PCDEA)--were tested on basilar and middle cerebral arteries of the dog in vitro and found to induce contraction in these blood vessels with a maximal contractile activity (i.e., intrinsic activity) similar to that of PCP. The concentration-effect curves of these compounds were found to be parallel to the curve of PCP (P less than 0.01). The relative potency was PCE greater than TCP greater than PCP greater than THP greater than PCDEA greater than ketamine. A PCP analog with no psychotomimetic activity, 1-piperidinocyclohexanecarbonitrile (PCC), did not induce the blood vessels to contract, nor did the opiate morphine. Three psychotomimetic benzomorphans--pentazocine, cyclazocine, and N-allylnorcyclazocine--were found to: (i) also produce contraction; and (ii) have concentration--effect curves parallel to the curve of PCP, but with reduced intrinsic activities (i.e., maximal tensions were lowered) compared to PCP. A kappa opiate, ethylketocyclazocine, relaxed the blood vessels in a dose-dependent manner. This study provides direct evidence for a distinct PCP receptor on cerebral blood vessels and suggests that certain benzomorphans may produce cerebral vasospasm via PCP-receptor interactions.
几种拟精神病性苯环己哌啶（PCP）类似物——N-乙基-1-苯基环己胺（PCE）、N-[1-(2-噻吩基)环己基]哌啶（TCP）、N-[1-(噻吩基)环己基]吡咯烷（THP）、氯胺酮和N,N-二甲基-1-苯基环己胺（PCDEA），在体外对犬的基底动脉和大脑中动脉进行了测试，发现它们能使这些血管收缩，其最大收缩活性（即内在活性）与PCP相似。发现这些化合物的浓度-效应曲线与PCP的曲线平行（P<0.01）。相对效价为PCE>TCP>PCP>THP>PCDEA>氯胺酮。一种无拟精神病活性的PCP类似物1-哌啶环己烷甲腈（PCC）以及阿片类药物吗啡均未引起血管收缩。发现三种拟精神病性苯并吗啡烷——喷他佐辛、环佐辛和N-烯丙基去甲环佐辛：（i）也会引起血管收缩；（ii）其浓度-效应曲线与PCP的曲线平行，但与PCP相比内在活性降低（即最大张力降低）。一种κ阿片类药物乙基酮环佐辛能以剂量依赖的方式使血管舒张。本研究为脑血管上存在独特的PCP受体提供了直接证据，并表明某些苯并吗啡烷可能通过与PCP受体相互作用而导致脑血管痉挛。
