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The Phencyclidine (PCP) Analog N-[1 -(2-Benzo(B)Thiophenyl) Cyclohexyl]Piperidine Shares Cocaine-Lik

The Phencyclidine (PCP) Analog N-[1 -(2-Benzo(B)Thiophenyl) Cyclohexyl]Piperidine Shares Cocaine-Lik

  1. Jasim
    Phencydidine (PCP) inhibits dopamine (DA) uptake and acts as a noncompetitive N-methyl-D-aspartate antagonist by binding to PCP receptors. The PCP analog N-[1-(2-benzo(b)thiophenyl) cyclohexyl]piperidine (BTCP, GK13) is a potent DA uptake inhibitor, but has low affinity for PCP receptors. The behavioral effects of BTCP were compared with those of PCP, ketamine, MK-801
    and cocaine. In mice, BTCP, like cocaine, produced locomotion, sniffing and gnawing; haloperidol blocked these effects. PCP, ketamine and MK-801 produced locomotion, sniffing, swaying and falling. PCP, ketamine and MK-801 produced generalization
    in rats discriminating either cocaine, PCP or MK-801 from saline. Like cocaine, BTCP produced generalization in cocaine-discriminating rats only; haloperidol partially antagonized this effect. In pigeons, PCP-like catalepsy was produced by ketamine and MK-801 , but not by BTCP. N-methyl-D-aspartate-induced convulsions in mice were antagonized by PCP, ketamine and MK-801, but not by BTCP or cocaine. Thus, BTCP shared only cocaine like behavioral effects with PCP, ketamine and MK-801 . A DA antagonist reduced the effects of BTCP. Therefore, the cocaine like behavioral effects of BTCP may be mediated primarily by DA uptake mechanisms. However, PCP receptors, but not DA uptake mechanisms, may mediate the cocaine-like behavioral effects of PCP, ketamine and MK-801 , because their order of potency in producing these effects (MK-801 > PCP > ketamine) is consistent with their potency order at PCP receptors, but not at DA uptake sites.