Domino E F, Gole D, Koek W
Department of Pharmacology, University of Michigan, Ann Arbor.
J Pharmacol Exp Ther. 1987 Oct;243(1):95-100.
Metaphit, a derivative of phencyclidine (PCP) differing by the meta substitution of an isothiocyanate group on the phenyl ring, was given into the lateral cerebral ventricle of mice alone and as a pretreatment to the subsequent i.p. injection of PCP and pentobarbital. Drug effects on motor performance as an index of neurologic impairment were quantified using the mouse platform test. The ED50 of metaphit to disrupt mouse platform behavior 5 min after i.c.v. administration was 0.48 mumol. An isobolographic analysis indicated that metaphit interacted additively with PCP and pentobarbital. Animals that recovered 24 or 48 hr after a large dose (1 mumol i.c.v.) of metaphit or phenylisothiocyanate, a nonspecific acylating control substance, were then given PCP (18.3 mumol/kg i.p.) or pentobarbital (76.7 mumol/kg i.p.). Both agents enhanced PCP-induced failure of mice to climb to the top of the platform. Metaphit also enhanced pentobarbital-induced failure of mice to climb to the top of the platform. No evidence was obtained that metaphit antagonized the behavioral effects of PCP in mice.
美他西泮，一种苯环己哌啶（PCP）的衍生物，其苯环上的异硫氰酸酯基团为间位取代，单独注入小鼠侧脑室，并作为预处理用于随后腹腔注射PCP和戊巴比妥。使用小鼠平台试验将药物对运动表现的影响作为神经功能损害的指标进行量化。脑室内给药5分钟后，美他西泮破坏小鼠平台行为的半数有效剂量（ED50）为0.48微摩尔。等效应线图分析表明，美他西泮与PCP和戊巴比妥呈相加作用。在给予大剂量（脑室内注射1微摩尔）美他西泮或苯异硫氰酸酯（一种非特异性酰化对照物质）24或48小时后恢复的动物，随后给予PCP（腹腔注射18.3微摩尔/千克）或戊巴比妥（腹腔注射76.7微摩尔/千克）。两种药物均增强了PCP诱导的小鼠无法爬到平台顶部的效应。美他西泮也增强了戊巴比妥诱导的小鼠无法爬到平台顶部的效应。未获得美他西泮拮抗PCP对小鼠行为影响的证据。
