The phencyclidine (PCP) analog N-[1-(2-benzo(B)thiophenyl) cyclohexyl]piperidine shares cocaine-like but not other characteristic behavioral effects with PCP, ketamine and MK-801.
Phencyclidine (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 greater than PCP greater than ketamine) is consistent with their potency order at PCP receptors, but not at DA uptake sites.
Koek
W
W
Neurobiology Division, FONDAX-Groupe de Recherche Servier, Puteaux, France.
Colpaert
F C
FC
Woods
J H
JH
Kamenka
J M
JM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D010856:Columbidae; D003913:Dextroamphetamine / Q000494:pharmacology; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004298:Dopamine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology*; D008774:Methylphenidate / Q000494:pharmacology; D051379:Mice; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D012640:Seizures / Q000139:chemically induced; D013329:Structure-Activity Relationship
D003986:Dibenzocycloheptenes; D008774:Methylphenidate; D007649:Ketamine; D016291:Dizocilpine Maleate; D003042:Cocaine; D010622:Phencyclidine; D006220:Haloperidol; D003913:Dextroamphetamine; D004298:Dopamine