Wang Y, Palmer M, Freedman R, Hoffer B, Mattson M V, Lessor R A, Rice K C, Jacobson A E
Proc Natl Acad Sci U S A. 1986 Apr;83(8):2724-7. doi: 10.1073/pnas.83.8.2724.
Metaphit (1-[1-(3-isothiocyanatophenyl)-cyclohexyl]piperidine), a derivative of the psychotomimetic drug phencyclidine (PCP), is postulated to bind irreversibly to PCP receptors. We examined here the electrophysiological interactions of metaphit with PCP in rat cerebellar cortex, since a specific effect of PCP on cerebellar neuronal circuitry has been shown. Metaphit, applied locally to Purkinje neurons by micropressure ejection through multibarreled micropipettes, has a reversible depressant action lasting for 5-20 min. Following this, PCP-induced inhibition is blocked with no recovery despite repeated applications of PCP for over an hour. This blockade was not seen unless the dose of metaphit was sufficient to transiently depress Purkinje neuron discharge. Metaphit does not antagonize inhibitory effects of locally applied norepinephrine or gamma-aminobutyric acid. This electrophysiological data suggests that metaphit is an irreversible antagonist of PCP in the cerebellum.
迈他普（1-[1-(3-异硫氰酸苯酯)-环己基]哌啶），一种拟精神病药物苯环己哌啶（PCP）的衍生物，被假定与PCP受体不可逆结合。鉴于已表明PCP对小脑神经元回路有特定作用，我们在此研究了迈他普与PCP在大鼠小脑皮质中的电生理相互作用。通过多管微电极微量压力喷射将迈他普局部应用于浦肯野神经元，其具有持续5至20分钟的可逆性抑制作用。在此之后，尽管反复应用PCP超过一小时，PCP诱导的抑制作用仍被阻断且无恢复。除非迈他普的剂量足以短暂抑制浦肯野神经元放电，否则不会出现这种阻断作用。迈他普不会拮抗局部应用去甲肾上腺素或γ-氨基丁酸的抑制作用。该电生理数据表明，迈他普是小脑中PCP的不可逆拮抗剂。
