Abstract
Phencylidine (PCP) is a major drug of abuse in the United States. It produces a toxic confusional psychosis in man. We show here that nanomolar to micromolar concentrations of PCP and behaviorally active congeners selectively block voltage-regulated noninactivating (or very slowly inactivating) presynaptic K channels in the brain. The rank order of potency for blockage of these K channels parallels both the relative ability of these agents to produce characteristic behavioral deficits in rats and their ability to displace [3H]PCP from its high-affinity binding sites in brain. In view of the enhanced voltage-gated Ca influx that would be expected to accompany blockage of presynaptic K channels, this mechanism could explain the excessive neurotransmitter release that is characteristic of PCP intoxication.
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Selected References
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