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)

The effects of diazepam, pentobarbital, and phencyclidine (PCP) were studied on punished and unpunished responding maintained by fixed-interval schedules before and during chronic administration of diazepam. Before chronic diazepam administration, increasing doses of diazepam and PCP increased and then decreased rates of both punished and unpunished responding. Increases in punished responding were larger than increases in unpunished responding. Pentobarbital only increased punished responding, while higher doses decreased both rates of punished and unpunished responding. During chronic diazepam administration, rates of punished and unpunished responding showed further increases with all three drugs and the dose-effect curves also shifted to the right. Analysis of local rates of responding within fixed-interval components suggested that increases in low rates early in the interval were responsible for the rate increases produced by these drugs before chronic diazepam administration. During chronic diazepam administration low rates early in the interval showed greater increases after all three drugs and their ability to produce rate-increasing effects extended further into the interval. The similar effects of these drugs before and during chronic diazepam administration suggests a similar mechanism despite the widely recognized differences in their interaction with receptors. This common mechanism may relate to rate-increasing effects more than to specific effects on punished responding.
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PMID:Effects of drugs on behavior before and during chronic diazepam administration. 139 83

In rats treated with phencyclidine (PCP) repeatedly (PCP 10 mg/kg per day for 14 days), the back-pedalling, head-weaving and turning induced by PCP were attenuated (tolerance), while PCP-induced sniffing, rearing and ambulation were potentiated (supersensitivity). The behavior induced by the direct and indirect serotonin (5-HT) agonists, 5-methoxy-N,N-dimethyltryptamine and p-chloroamphetamine, was attenuated, while the sniffing, rearing or licking induced by the direct and indirect dopamine (DA) agonists, apomorphine and methamphetamine, were potentiated in the chronic PCP-treated rats. The DA and 5-HT contents in the nucleus accumbens and the ratio of HVA to DA in the striatum increased following the repeated PCP administration. Pentobarbital-induced sleep time did not change in the chronic PCP-treated rats as compared with the control rats. In addition, there was no significant difference between the disappearance rate of PCP in the brain of the rats treated with PCP repeatedly and the rate in the control rats. These results suggest that functional changes in the dopaminergic and serotonergic neuronal systems develop on repeated administration of PCP but that such changes do not develop in the hepatic drug-metabolizing system. In addition, tolerance develops in the serotonergic neuronal system while supersensitivity develops in the dopaminergic neuronal system. Biochemical findings suggest that increased mesolimbic dopaminergic neuronal function plays an important role in the development of the supersensitivity.
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PMID:Development of tolerance and supersensitivity to phencyclidine in rats after repeated administration of phencyclidine. 356 23

The influence of phencyclidine (PCP) on the tissue distribution of pentobarbital in male Swiss mice (20-25 g) was investigated. Animals pretreated with PCP (179 mumol/kg/day) for 4 days, i.p., were administered pentobarbital (60 mg/kg, i.p.) 24 h after the PCP injection, sacrificed at various time intervals, and tissues (serum, brain, liver and kidney) were collected. Pentobarbital levels in tissues were determined by the gas liquid chromatography. When compared to the control group, PCP treatment decreased the pentobarbital level by 68% in liver and increased the level by 97% in kidney at 45 min post-injection. No significant change in serum and brain pentobarbital level was noted with either group. These data indicate that PCP influences the translocation of pentobarbital.
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PMID:Influence of phencyclidine on the translocation of pentobarbital in mice. 671 May 39

Several pharmacologically distinct sites are known to modulate the N-methyl-D-aspartate (NMDA) receptor/ion complex, including a site within the ion channel which binds uncompetitive antagonists like phencyclidine (PCP) or dizocilpine. Glycine acts as a co-agonist for activation of the NMDA receptor complex through a strychnine-insensitive receptor, which is a potential target for novel therapeutic agents (e.g., anticonvulsants, antidepressants). We evaluated the behavioral effects of glycine receptor ligands in rats trained to discriminate either dizocilpine or PCP from saline, to predict whether glycine receptor ligands might induce undesirable PCP-like subjective effects in humans. Dizocilpine ([+]-MK-801), (-)-MK-801 and PCP produced dose-dependent substitution in these rats with potencies in accord with NMDA receptor affinity. Pentobarbital and drugs acting at other sites of the NMDA receptor, including competitive antagonists (NPC 12626 and LY 274614) and the polyamine antagonist, ifenprodil, did not substitute for either dizocilpine or PCP. In contrast to the uncompetitive antagonists like PCP, none of the strychnine-insensitive glycine receptor ligands substituted. Neither the full agonist, glycine; the partial agonists, 1-amino-1-cyclopropanecarboxylic acid, D-cycloserine or (+)-3-amino-1-hydroxypyrrolid-2-one; nor the antagonists, 7-chloro and 5,7-dichlorokynurenic acid, mimicked the discriminative stimulus effects of dizocilpine or PCP. Further, co-administration of 1-amino-1-cyclopropanecarboxylic acid did not significantly enhance the discriminative stimulus effects of dizocilpine. Intracerebroventricular administration of D-serine, a selective agonist of the strychnine-insensitive glycine receptor, neither mimicked nor blocked the discriminative stimulus effects of PCP. These data suggest that functional antagonists of the strychnine-insensitive glycine receptor may be devoid of the subjective side effects characteristic of NMDA channel ligands.
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PMID:Effects of strychnine-insensitive glycine receptor ligands in rats discriminating dizocilpine or phencyclidine from saline. 899 80

N-methyl-D-aspartate (NMDA) glutamate (Glu) receptor antagonists (eg MK-801, ketamine, phencyclidine [PCP]) injure cerebrocortical neurons in the posterior cingulate and retrosplenial cortex (PC/RSC). We have proposed that the neurotoxic action of these agents is mediated in part by a complex polysynaptic mechanism involving an interference in GABAergic inhibition resulting in excessive release of acetylcholine (ACh). Previously we have found that the systemic injection of GABAergic agents and alpha2-adrenergic agonists can block this neurotoxicity. In the present study we tested the hypothesis that NMDA antagonists trigger release of ACh in PC/RSC and that this action of NMDA antagonists is suppressed by GABAergic agents or alpha2-adrenergic agonists. The effect of MK-801 and ketamine on PC/RSC ACh output (and the ability of pentobarbital, diazepam and clonidine to modify MK-801-induced ACh release) was studied in adult female rats using in vivo microdialysis. Both MK-801 and ketamine caused a significant rise in PC/RSC ACh output compared to basal levels. Pentobarbital, diazepam and clonidine suppressed MK-801's effect on ACh release. Exploratory studies indicated that the site of action of these agents was outside of the PC/RSC. The microdialysis results are consistent with several aspects of the circuitry proposed to mediate the neurotoxic action of NMDA antagonists.
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PMID:Excessive cerebrocortical release of acetylcholine induced by NMDA antagonists is reduced by GABAergic and alpha2-adrenergic agonists. 1048 51

There is in vitro evidence that some of the effects of abused volatile solvents may be produced by actions at the NMDA receptor. In addition, some solvents produce phencyclidine-like discriminative stimulus effects. The major goal of the present study was to further compare abused solvents to NMDA antagonists by testing them in two strains of mice trained to discriminate 0.17 mg/kg of the very selective uncompetitive NMDA antagonist, dizocilpine, from saline and contrast those results with several GABA(A)-positive modulators, PCP and ethanol. The results indicated that the discriminative stimulus produced by 0.17 mg/kg dizocilpine was highly specific in both mouse strains. PCP produced 91% dizocilpine-lever responding in C57BL/6J mice, but only 56% dizocilpine-lever responding in DBA/2J mice. Pentobarbital, midazolam and ethanol produced at least some overlap in discriminative stimulus effects with dizocilpine in one or both mouse strains. In contrast, toluene, 1,1,1-trichloroethane (TCE), xylene and methoxyflurane produced saline-appropriate responding almost exclusively. These data indicate that, at least under the specific conditions tested, abused volatile solvents do not have substantial dizocilpine-like discriminative stimulus effects in either C57BL/6J or DBA/2J mice, providing little support that NMDA antagonism plays a central role in the production of this abuse-related effect.
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PMID:Effects of abused inhalants and GABA-positive modulators in dizocilpine discriminating inbred mice. 1550 Dec 97