Metaphit, a proposed phencyclidine (PCP) antagonist, prevents PCP-induced locomotor behavior through mechanisms unrelated to specific blockade of PCP receptors.
Metaphit, a proposed phencyclidine (PCP) antagonist, prevents PCP-induced locomotor behavior through mechanisms unrelated to specific blockade of PCP receptors.
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Metaphit 是一种拟议的苯环己哌啶 (PCP) 拮抗剂，通过与特定阻断 PCP 受体无关的机制来防止 PCP 诱导的运动行为。
DOI：
10.1016/0014-2999(87)90283-4
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发表时间：
1987
影响因子：
5
通讯作者：
Rice,KC
中科院分区：
文献类型：
--
作者：
French,ED;Jacobson,AE;Rice,KC
Metaphit是苯环己哌啶（PCP）的衍生物，可与大鼠脑内PCP受体位点不可逆结合，被认为是一种潜在的特异性PCP拮抗剂。然而，在整个动物研究中，metaphit已被证明具有拮抗剂或PCP样作用，这取决于所使用的动物物种和评估的实验变量。在本研究中，PCP产生多动症的能力进行了评估，在大鼠静脉内，脑室内或脑内注射metaphit预处理后。然而，静脉内和脑室内metaphit预处理未能改变PCP的运动刺激作用，直接注射metaphit到延髓核导致PCP诱导的多动症的剂量依赖性减少。该结果也被等摩尔浓度的PCP内注射所模仿，但不是由局部麻醉剂普鲁卡因。此外，intra-alcohens metaphit防止d-苯丙胺诱导的多动症，也耗尽显着alcohens多巴胺含量;效果没有看到脑内PCP管理后。这些结果表明，metaphit产生的PCP诱导的运动活动的功能性拮抗作用，通过突触前机制无关的PCP受体的特异性封锁。
Metaphit, a derivative of phencyclidine (PCP) which irreversibly binds to a population of PCP receptor sites in rat brain, has been considered as a potentially specific PCP antagonist. In whole animal studies, however, metaphit has been shown to have either antagonist or PCP-like actions depending upon the animal species used and the experimental variable evaluated. In the present study, the ability of PCP to produce hyperactivity was assessed in rats following pretreatment with intravenous, intraventricular or intracerebral injections of metaphit. Whereas, intravenous and intraventricular metaphit pretreatment failed to alter the locomotor stimulatory effects of PCP, direct injections of metaphit into the nucleus accumbens resulted in a dose-dependent reduction of PCP-induced hyperactivity. This result also was mimicked by intra-accumbens injections of equimolar concentrations of PCP, but not by the local anesthetic procaine. Additionally, intra-accumbens metaphit prevented d-amphetamine-induced hyperactivity and also depleted significantly accumbens dopamine content; effects not seen after intracerebral PCP administration. These results suggest that metaphit produces a functional antagonism of PCP-induced locomotor activity through presynaptic mechanisms unrelated to specific blockade of PCP receptors.