Wang Y, Palmer M R, Freedman R, Rice K C, Lessor R A, Jacobson A E, Hoffer B J
J Neurosci. 1986 Nov;6(11):3189-96. doi: 10.1523/JNEUROSCI.06-11-03189.1986.
Metaphit, 1-(1-(3-isothiocyanatophenyl) cyclohexyl) piperidine, an analog of phencyclidine (PCP) has been shown previously to selectively block PCP receptors and to irreversibly antagonize the depressant effect of PCP in cerebellum. In this study, we examined the electrophysiological interactions of metaphit and naloxone with stereoisomers of cyclazocine, an agent known to have analgesic and psychotomimetic activity in behavioral studies, effects that have been ascribed to opiate and PCP receptor activity. A dose-dependent and reversible slowing of Purkinje neuron discharge was seen with local application of (+)- or (-)-cyclazocine. We found that the blockade of (-)-cyclazocine effects required both high doses of naloxone and the presence of metaphit, whereas the responses to (+)-cyclazocine were blocked by metaphit alone on most cerebellar Purkinje neurons. These findings suggest that the depressant reaction of (+)-cyclazocine in cerebellar Purkinje neurons is primarily mediated through PCP receptors. (-)-Cyclazocine responses, on the other hand, appear to be due to activity at both PCP and kappa opioid receptors.
美他西泮，1-(1-(3-异硫氰酸苯酯基)环己基)哌啶，是苯环己哌啶（PCP）的类似物，先前已证明其能选择性阻断PCP受体，并不可逆地拮抗PCP对小脑的抑制作用。在本研究中，我们研究了美他西泮和纳洛酮与环唑辛立体异构体的电生理相互作用，环唑辛在行为学研究中已知具有镇痛和拟精神病活性，这些作用归因于阿片受体和PCP受体活性。局部应用(+)-或(-)-环唑辛可观察到浦肯野神经元放电呈剂量依赖性且可逆性减慢。我们发现，阻断(-)-环唑辛的作用既需要高剂量的纳洛酮，也需要美他西泮的存在，而在大多数小脑浦肯野神经元上，单独使用美他西泮就能阻断对(+)-环唑辛的反应。这些发现表明，(+)-环唑辛对小脑浦肯野神经元的抑制反应主要通过PCP受体介导。另一方面，(-)-环唑辛的反应似乎是由于PCP受体和κ阿片受体的活性所致。
