Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.16.2 (PCP)
3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phencyclidine binds with high affinity to both PCP and sigma receptors. We investigated whether the clonal cell line PC12 expressed either of these receptors, and found that these cells contain a haloperidol-sensitive (+)-[3H]3-PPP binding site with a KD of 56 nM, but no PCP binding sites. The (+)3-PPP binding sites in PC12 cells displayed a reversed stereoselectivity for the benzomorphan opiates compared to CNS sigma receptors. Neither nerve growth factor nor sodium butyrate treatment affected the expression of either (+)-3-PPP or TCP binding sites in PC12 cells.
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PMID:Expression of (+)-3-PPP binding sites in the PC12 pheochromocytoma cell line. 256 79

Phencyclidine is a widely used drug of abuse and is known to produce a wide variety of psychoactive effects. PCP abuse by pregnant women has been reported to result in the birth of infants exhibiting irritability, jitteriness and hyperactivity with high pitched cries. The present study was designed to evaluate the distribution of PCP in the maternal and fetal brain and the neurochemical effects produced by gestational exposure. Pregnant Sprague-Dawley rats were treated sc with 5 mg/kg PCP on 3 consecutive days (GD 9-11, 12-14, 15-16, or 18-20). On gestational day (GD) 21 all rats were killed by decapitation and maternal and fetal blood was collected for PCP analysis. Brains were dissected from dams and fetuses for PCP and neurochemical analyses. On GD 21 after exposure on GD 18-20, the fetal: maternal ratio of brain PCP concentrations was 11:1. PCP exposure on GD 12-14, 15-17, and 18-20 significantly decreased fetal brain PCP binding sites on GD 21, whereas maternal values were unchanged. Fetal dopaminergic and muscarinic cholinergic receptor binding and neurotransmitter concentrations were unaffected by prenatal PCP exposure. These data demonstrated that maternal PCP exposure resulted in prolonged exposure of the developing CNS and also indicated that gestational exposure to PCP decreased high affinity binding sites of PCP in term fetal brain.
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PMID:Effects of gestational exposure to phencyclidine: distribution and neurochemical alterations in maternal and fetal brain. 257 1

Phencyclidine (PCP), a dissociative anesthetic and widely abused psychotomimetic drug, and MK-801, a potent PCP receptor ligand, have neuroprotective properties stemming from their ability to antagonize the excitotoxic actions of endogenous excitatory amino acids such as glutamate and aspartate. There is growing interest in the potential application of these compounds in the treatment of neurological disorders. However, there is an apparent neurotoxic effect of PCP and related agents (MK-801, tiletamine, and ketamine), which has heretofore been overlooked: these drugs induce acute pathomorphological changes in specific populations of brain neurons when administered subcutaneously to adult rats in relatively low doses. These findings raise new questions regarding the safety of these agents in the clinical management of neurodegenerative diseases and reinforce concerns about the potential risks associated with illicit use of PCP.
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PMID:Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. 240 96

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.
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PMID: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. 267 16

Phencyclidine (PCP), in doses of 0.25, 0.35, and 0.45 mg/kg, was administered systemically to male Sprague-Dawley rats in order to determine if a positive conditioned place preference (CPP) could be achieved. Other subjects received systemic injections of morphine, 4.0 mg/kg, as a standard for comparison. At testing, rats receiving 0.45 mg/kg PCP showed a positive CPP compared to controls, as did rats receiving morphine. Previous research had shown that larger doses of PCP and prolonged times after PCP administration produced aversion as indexed by CPP testing. The narrow dose range and short time span in which PCP's positively reinforcing properties are apt to emerge may be related to PCP's psychotomimetic potential and to its ability to sustain its own intake even though aversive effects are often manifest.
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PMID:PCP and conditioned place preferences. 281 67

Phencyclidine (PCP)-induced behaviors were compared with 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)- and p-chloroamphetamine-induced behaviors in rats pretreated with ritanserin or 5,7-dihydroxytryptamine (5,7-DHT) in order to investigate whether PCP interacts with 5-hydroxytryptamine2 (5-HT2) receptors. Head-twitch and wet-dog shake induced by p-chloroamphetamine, a 5-HT releaser, and head-twitch induced by PCP were blocked completely by pretreatment with ritanserin, a specific 5-HT2 receptor blocker, but other behaviors induced by p-chloroamphetamine, PCP and 5-MeODMT, a 5-HT agonist, were not. The intensity of head-weaving, turning, backpedalling and hind-limb abduction induced by 5-MeODMT and the intensity of head-weaving, turning and head-twitch induced by PCP were markedly greater in the rats 2 weeks after the 5,7-DHT, a 5-HT neurotoxin-injection. Contrarily, 5-HT-mediated behaviors induced by p-chloroamphetamine were attenuated in the 5,7-DHT-treated rats. 5,7-DHT-treatment increased the number of 5-HT1 ([3H]-5-HT), 5-HT2 ([3H]ketanserin) and PCP ([3H]PCP) binding sites in the synaptic membrane of rat brain, but decreased the brain level of 5-HT (41% of control). These results may indicate that PCP as a 5-HT2 agonist induces head-twitch via 5-HT2 receptors, and that PCP induces head-weaving and turning via 5-HT1 receptors and/or some other mechanisms in rats.
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PMID:Potentiation in phencyclidine-induced serotonin-mediated behaviors after intracerebroventricular administration of 5,7-dihydroxytryptamine in rats. 282 56

Phencyclidine (PCP) and related noncompetitive antagonists of N-methyl-D-aspartate (NMDA) receptor neuroexcitation were tested for their ability to attenuate either NMDA- or hypoxia-induced neuronal loss in dissociated cell cultures prepared from mouse neocortex. 10 microM PCP or MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] selectively blocked the neurotoxicity produced by application of NMDA or the endogenous NMDA agonist quinolinate, without altering kainate or quisqualate neurotoxicity. Blockade of NMDA toxicity was concentration-dependent in the submicromolar and micromolar range, with a potency order (MK-801 greater than PCP greater than SKF 10,047 greater than pentazocine) consistent with primary mediation at PCP sites rather than at sigma sites. PCP reduced the toxicity of high NMDA concentrations, consistent with a noncompetitive mechanism of antagonism. PCP ligands also potently attenuated neuronal injury after exposure of the cultures to hypoxia. The effective concentrations and drug potency order for blockade of hypoxic injury were quantitatively similar to results obtained against the application of exogenous NMDA. These observations provide further support for the hypothesis that excessive activation of NMDA receptors may participate importantly in the pathogenesis of hypoxic brain injury.
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PMID:Phencyclidine receptor ligands attenuate cortical neuronal injury after N-methyl-D-aspartate exposure or hypoxia. 283 3

Phencyclidine (PCP) has been reported to suppress a variety of immune functions in vitro. Because PCP binds with high affinity to both PCP and sigma receptors, the identity of the receptor(s) mediating the immunological effects of PCP is unknown. The aim of the present study was to identify and characterize the sites of PCP action (sigma and/or PCP receptors) in human peripheral blood leukocytes (PBL) using [3H]haloperidol or 1,3 di(2-([5-3H]tolyl)guanidine ([3H]DTG) to specifically label sigma receptors and 3,4-[3H]-(N)-[1-(2-thienyl)-cyclohexyl]-piperidine ([3H]TCP) to specifically label PCP receptors. [3H]Haloperidol binding was saturable and of high affinity with comparable KD values in human PBL (0.44 +/- 0.10 nM) and rat cerebellum (0.51 +/- 0.09 nM). Similarly, [3H]DTG binding was saturable with comparable KD values of 29.5 +/- 3.5 and 26.4 +/- 3.6 nM in rat cerebellum and human PBL, respectively. In contrast, there was a notable absence of [3H]TCP-labeled PCP receptors in human PBL and rat cerebellum. In competition studies, the pharmacologic profile of [3H]haloperidol-labeled sigma receptors in human PBL was virtually identical with that in rat cerebellum (slope, 0.87; correlation coefficient, 0.96); the rank order of potency of competing drugs was haloperidol greater than l-butaclamol = pentazocine greater than d-3-(hydroxyphenyl)-N-(1-propyl)-piperidine greater than DTG = d-butaclamol = d-SKF 10,047 greater than levallorphan greater than or equal to PCP greater than or equal to l-SKF 10,047 greater than TCP greater than MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Initial identification and characterization of sigma receptors on human peripheral blood leukocytes. 284 60

Phencyclidine (PCP) was examined for its ability to modulate histamine release from rat brain slices labeled with L-[3H]histidine. PCP failed to mimic but completely reversed the autoinhibitory effect of histamine at H3-receptors with an apparent Ki value of 13 +/- 3 microM. A direct interaction of PCP with H3-autoreceptors rather than PCP or sigma receptor sites was confirmed by binding studies. PCP inhibited the binding of [3H](R)alpha-methylhistamine to H3-receptor sites in rat cerebral membranes with a Ki value of 25 +/- 2 microM. It is concluded that PCP is a H3-receptor antagonist of moderate potency.
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PMID:Phencyclidine blocks histamine H3-receptors in rat brain. 285 72

Phencyclidine (PCP) was tested on the metathoracic tibialis muscles of Locusta migratoria. In physiological solution, the peak amplitude of the excitatory postsynaptic currents (EPSCs) evoked by nerve stimulation was linearly related to membrane potential between -50 and -150 mV. The decay time constant of the EPSC (tau EPSC) was exponentially dependent on voltage and decreased with hyperpolarization. The membrane potential change required to produce an e-fold change in tau EPSC was 315 mV. PCP (5-40 microM) produced a concentration-dependent depression of both EPSC peak amplitude and tau EPSC. A slight nonlinearity in the current-voltage relationship could be discerned at high concentrations of PCP. The shortening of the decay time constant of EPSC (tau EPSC) occurred without significant change in the voltage sensitivity observed under control conditions. Under all experimental conditions, the decay of the EPSCs remained a single exponential of time. Fluctuation analysis indicated that 5 microM PCP shortens the lifetime of the glutamate-activated channels by 25.7 +/- 3%. PCP (10-80 microM) did not induced desensitization of the glutamate receptors. These results suggest that PCP interacts with the open conformation of ion channels activated by the glutamate receptor.
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PMID:Phencyclidine (PCP) blocks glutamate-activated postsynaptic currents. 286 72


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