Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many PCP-like drugs interact with at least two types of binding sites in the CNS, one of which is linked to excitatory amino acid transmission and the other with an unknown function. The present experiments were designed to further clarify the mechanism of action of drugs in this class. Assessment was made of the effects of PCP, MK-801, (+)-pentazocine, (+)- and (-)-N-allyl-normetazocine (NANM), (+)-amphetamine and BMY-14802 in rats responding under a multiple timeout 600 s (TO), differential reinforcement of low rates 10 s (DRL), fixed ratio (FR) 10 schedule of reinforcement. The effects of the PCP-receptor selective drug MK-801 were compared to those of the mixed sigma/PCP drug (+)-NANM after each were combined with doses of (+)-pentazocine, PCP, BMY-14802, and (+)-amphetamine. MK-801 was also tested in combination with (+)-NANM, as was PCP with BMY-14802. When administered alone, MK-801, PCP, (+)-NANM, (+)-pentazocine, and (+)-amphetamine increased rates of responding under the DRL component of the multiple schedule. The drugs tested generally produced decreases in rates of responding under the FR component. (+)-Pentazocine and BMY-14802 did not modify the effects of (+)-NANM or of MK-801. PCP enhanced the effects of MK-801 and (+)-NANM, and (+)-amphetamine enhanced the effects of MK-801 but not of (+)-NANM. BMY-14802 attenuated the effects of PCP. Taken together, these data suggest similarities as well as some differences in the pharmacologic activities of MK-801 and (+)-NANM and PCP.
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PMID:Interaction of sigma and PCP-like drugs on operant behaviors in the rat. 141 Jan 31

Several phencyclidine (PCP) and sigma receptor ligands were examined for their effects on a single trial passive avoidance test in rats. Rats were administered the PCP receptor ligands (+)-5-methyl-10,11-dihydro-5Hdibenzo[a,d]cyclohepten-5,10-im ine maleate (MK-801), PCP, ketamine or the sigma receptor ligands (+)-N-allylnormetazocine ((+)-NANM), (+)-pentazocine, (+)-3-(3-hydroxyphenyl)-N-n-propylpiperidine ((+)-3-PPP) or 1,3-Di(2-[5-3H]tolyl)guanidine (DTG) subcutaneously prior to acquisition of the passive avoidance response, and tested 24 h later for retention. MK-801 (0.1-0.3 mg/kg), PCP (0.54-1.7 mg/kg), ketamine (10.0-17.2 mg/kg) and (+)-N-allylnormetazocine (5.4-10.0 mg/kg) produced significant memory deficits. (+)-Pentazocine (54 mg/kg) and (+)-3-PPP (30 mg/kg) also produced retention deficits, but at significantly higher doses. DTG (0.3-3.0 mg/kg s.c.) had no effect on retention. There was a positive correlation between production of retention deficits and the compounds' PCP receptor binding affinity. The results suggest that the sigma receptor is not involved in learning the passive avoidance response.
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PMID:Differential effects of sigma and phencyclidine receptor ligands on learning. 216 53

(+)-Pentazocine, a potent sigma ligand that lacks affinity for PCP receptors, produced dose-dependent contralateral circling behavior following microinjections in the substantia nigra of rats. This effect was attenuated by 6-hydroxydopamine (6-OHDA) lesions of ascending dopamine neurons and enhanced by systemic injections of amphetamine, 6-OHDA lesions also attenuated the circling produced by another selective sigma ligand, 1,3-di-o-tolylguanidine (DTG). These findings suggest that sigma receptors are involved in the neural control of movement and the regulation of the ascending dopamine system. Since all typical antipsychotic drugs tested bind to sigma receptors with Ki values less than 1 microM, these findings further suggest that sigma receptors may mediate some of the motor side effects of antipsychotic drug therapy.
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PMID:Motor effects of two sigma ligands mediated by nigrostriatal dopamine neurons. 255 20

Research on the sigma receptor, a binding site associated with drug-induced psychotomimetic behaviors, has been hampered because most sigma agonists also interact with the phencyclidine (PCP) receptor. (+)-Pentazocine, a human psychotogen, is a selective sigma receptor ligand. To demonstrate sigma receptor activities, we studied the behavioral and electrophysiologic actions for (+)-pentazocine. In the behavioral drug discrimination procedure in which rats were trained to discriminate between 2.0 mg/kg (5.59 mumol/kg) (+)-pentazocine and saline, (+)-pentazocine produced dose-related increases in the percentage of trials completed on the (+)-pentazocine lever. At a dose of 1.0 mg/kg (3.29 mumol/kg) (+)-N-allylnormetazocine generalized completely to (+)-pentazocine. By contrast, PCP only partially generalized. In the visual evoked potential test, these compounds produced a significant dose-dependent slowing of the N2 latency. This response was prevented by haloperidol pretreatment. These results demonstrate pharmacologic actions for the selective sigma receptor ligand (+)-pentazocine and suggest some overlapping pharmacologic properties of the sigma and PCP receptor sites despite differences in central nervous system distribution.
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PMID:Biochemical, behavioral, and electrophysiologic actions of the selective sigma receptor ligand (+)-pentazocine. 285 2

Repeated administration of psychomotor stimulants such as amphetamine and cocaine, and psychotomimetics such as phencyclidine, produce progressively enhanced behavioral effects, a phenomenon known as behavioral sensitization. Little is known about the effects of repeated treatment with sigma ligands on locomotor activity. The present research determined the psychomotor stimulant effects of the sigma ligand (+)pentazocine and its enantiomer; and investigated whether reciprocal cross-sensitization occurs between them and PCP-induced locomotor activity and ambulation. Adult female Sprague-Dawley rats were used. Total locomotor activity and ambulation were assessed with an automated photoelectric system. Acute (+) or (-)pentazocine given IP produced slight but insignificant locomotor stimulant effects. Repeated administration of (+)pentazocine failed to produce behavioral sensitization. However, four repeated injections of (-)pentazocine or PCP produced behavioral sensitization. (-)Pentazocine sensitized rats showed cross-sensitization to PCP-induced locomotion and ambulation. Furthermore, PCP sensitized rats showed cross-sensitization to (-)pentazocine-induced locomotion and ambulation. These findings suggest that (+) and (-)pentazocine act at different receptor sites. (-)Pentazocine is more similar to PCP in producing locomotor stimulant effects.
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PMID:Cross-sensitization between phencyclidine and (-) but not (+) pentazocine. 905 76

Phencyclidine (PCP) is a compound that results in abnormal human behavior and has been proposed as a chemical model for schizophrenia. It was hypothesized that PCP induction of the immediate-early gene, c-fos, should be seen in areas associated with emotional behavior, such as the cortex and limbic system. It was also proposed that PCP may induce c-fos via the sigma receptor. PCP and two sigma ligands, 1,3-di(2-tolyl)guanidine (DTG) and pentazocine, were shown to induce c-fos in similar patterns. The three compounds abundantly induced c-fos in the cingulate, parietal, and piriform cortices and the midline structures of the thalamus and hypothalamus. Neither PCP nor the sigma ligands induced c-fos in the hippocampus. This suggests that PCP binding at NMDA receptors does not result in significant c-fos induction. Rimcazole, a putative sigma2 receptor antagonist, and other sigma ligands have been shown to ameliorate PCP stereotypic behavior. Rimcazole inhibited PCP c-fos induction in the cingulate and parietal cortices and DTG c-fos induction in the cingulate cortex. DTG shows both sigma1 and sigma2 binding affinity. Rimcazole failed to inhibit pentazocine c-fos induction. Pentazocine binds only to sigma1 receptors. This suggests that PCP may produce a significant fraction of its c-fos induction via sigma2 receptors.
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PMID:Phencyclidine (PCP) acts at sigma sites to induce c-fos gene expression. 920 33

Phencyclidine (PCP) binds to many sites in brain, including PCP receptors located within the N-methyl-D-aspartate (NMDA) receptor-operated cation channel and sigma (sigma) receptors. In this study, we compare mechanisms by which PCP, dizocilpine (MK-801), the prototypical sigma receptor agonist (+)-pentazocine, and the proposed endogenous sigma receptor ligand neuropeptide Y regulate potassium (K(+))-stimulated [3H]dopamine release from slices of rat nucleus accumbens. (+)-Pentazocine inhibits K(+)-stimulated [3H]dopamine release, and neuropeptide Y enhances it. Both effects are blocked by sigma(1) and neuropeptide Y receptor antagonists, suggesting possible inverse agonism at a subpopulation of sigma/neuropeptide Y receptors. In contrast, PCP and MK-801 both enhance K(+)-stimulated [3H]dopamine release via sigma(1) and sigma(2) receptor subtypes, as demonstrated by antagonist sensitivity. Regulation of release by both (+)-pentazocine and neuropeptide Y persists in the presence of tetrodotoxin suggests that the sigma/neuropeptide Y receptors mediating the modulation are located presynaptically on dopaminergic nerve terminals, but tetrodotoxin eliminates regulation by PCP and MK-801, suggesting that receptors mediating their effects are located upstream from dopaminergic nerve terminals.
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PMID:Phencyclidine and dizocilpine modulate dopamine release from rat nucleus accumbens via sigma receptors. 1061 64