Shannon H E
J Pharmacol Exp Ther. 1982 Jul;222(1):146-51.
The purpose of the present experiments was to evaluate the phencyclidine (PCP)-like discriminative stimulus properties of narcotic derivatives in the rat. Rats were trained to discriminate between saline and 3.0 mg/kg of PCP in a two-choice, shock-avoidance procedure. PCP-like stimulus control of behavior was produced by (in order of relative molar potency): l-cyclazocine greater than PCP greater than dl-cyclazocine greater than SKF 10,047 greater than MeO-cyclazocine greater than dextrorphan greater than d-cyclazocine. Metazocine and levalorphan also occasioned appreciable percentages of PCP-appropriate responding. Ten other narcotic derivatives, including pentazocine and nalorphine, occasioned only saline-appropriate responding. Among enantiomeric pairs, levocyclazocine was more potent than dextrocyclazocine, and dextrorphan but not levorphanol produced PCP-like discriminative effects. The specific narcotic antagonist naloxone failed to antagonize these PCP-like effects but rather increased the relative potency of cyclazocine and "unmasked" PCP-like effects of higher doses of metazocine. These results demonstrate that PCP and selected narcotic derivatives have similar components of action which appear to be mediated by sigma receptors rather than receptors which subserve the characteristic opioid actions of narcotic analgesics.
本实验的目的是评估麻醉性衍生物在大鼠体内的苯环利定（PCP）样辨别刺激特性。在双选择、电击回避程序中，训练大鼠区分生理盐水和3.0mg/kg的PCP。产生PCP样行为刺激控制作用的物质（按相对摩尔效力排序）为：左旋环唑辛＞PCP＞消旋环唑辛＞SKF 10,047＞甲氧基环唑辛＞右啡烷＞右旋环唑辛。美他佐辛和左啡诺也引发了相当比例的与PCP相符的反应。包括喷他佐辛和烯丙吗啡在内的其他10种麻醉性衍生物仅引发了与生理盐水相符的反应。在对映体对中，左旋环唑辛比右旋环唑辛更有效，右啡烷而非左啡诺产生了PCP样辨别效应。特异性麻醉拮抗剂纳洛酮未能拮抗这些PCP样效应，反而增加了环唑辛的相对效力，并“揭示”了高剂量美他佐辛的PCP样效应。这些结果表明，PCP和选定的麻醉性衍生物具有相似的作用成分，这些成分似乎是由σ受体介导的，而非介导麻醉性镇痛药典型阿片样作用的受体。
