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)

The psychotomimetic drug 1-(1-phenylcyclohexyl) piperidine (PCP, phencyclidine) was found to cause a deficit in the gating of the response of the hippocampal neuron to repeated auditory stimuli, which is similar to a particular physiological feature observed in human psychosis. Other drugs, with sigma agonist and/or N-methyl-D-aspartate (NMDA) antagonist effects, were administered and their ability to cause a loss of auditory gating was compared to that of PCP. The rank order of effectiveness was levoxodrol > PCP and (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801) > N-allylnormetazocine (SKF 10047) > dexoxodrol > 3-(+/-)2-carboxypiperazine-4-yl) propyl-1-phosphonate (CPP). Further studies of two of the drugs, PCP and MK-801, showed that selective lesioning of the noradrenergic input with the neurotoxin DSP4, as well as less selective depletion of monoamines with reserpine, blocked the loss of gating. Phencyclidine, and other drugs with the same spectrum of action, most likely disrupt gating by increasing noradrenergic activity through a sigma mechanism.
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PMID:Phencyclidine and auditory sensory gating in the hippocampus of the rat. 143 86

Acute cerebral ischemia and reperfusion injury of rabbits was produced by permanently occluding the vertebral arteries and temporarily clamping the common carotid arteries for 30 min. Phencyclidine [1-(phenylcyclohexyl)piperidine, PCP] 40-80 micrograms.kg-1 icv 30 min before ischemia significantly attenuated the decrease of the total power of electroencephalogram (EEG) within 30 min of ischemia and improved the recovery of brain electric activity following reperfusion. PCP 20-80 micrograms.kg-1 dose-dependently suppressed the creatine kinase (CK) release during cerebral ischemia and reperfusion, and PCP 40-80 micrograms.kg-1 reduced brain ischemic damage. These improvements indicated that PCP has protective effects on acute cerebral ischemia and reperfusion injury.
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PMID:Neuroprotective effects of phencyclidine on acute cerebral ischemia and reperfusion injury of rabbits. 144 2

Phencyclidine (PCP) acts as an indirect dopamine (DA) agonist by inhibiting the neuronal reuptake of DA, while it also works as a N-methyl-D-aspartate (NMDA) antagonist. Aiming to investigate characteristics of these two properties of PCP in the same experimental system, the effects of PCP on spontaneous and NMDA-induced efflux of DA from superfused slices of the striatum of the rat were examined. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the samples of superfusate were extracted by alumina extraction and measured by high-performance liquid chromatography with electrochemical detection (HPLC-EC). Phencyclidine at concentrations greater than 1 microM, produced a concentration-dependent increase of the spontaneous efflux of DA. The efflux of DOPAC was also concentration-dependently increased by PCP. However, PCP inhibited the efflux of DA induced by NMDA, even at a small concentration (0.1 microM), which did not alter the spontaneous efflux of the transmitter. The mode of the inhibition by PCP was shown to be noncompetitive, with an estimated IC50 value of 280 nM. These results suggest that PCP, at small concentrations, reduces the synaptic levels of DA by blocking the facilitating effect of endogenous glutamate on the release of DA and, at slightly greater concentrations, the drug also works as an indirect DA agonist, to increase the levels of the transmitter in the synaptic clefts. The clinical significance of the dual effects of PCP is discussed in relation with the unique schizophrenomimetic property of PCP.
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PMID:Effect of phencyclidine on spontaneous and N-methyl-D-aspartate (NMDA)-induced efflux of dopamine from superfused slices of rat striatum. 152 97

Whole blood samples were collected from arrested D. U. I. subjects in two locations, by the U. S. Park Police (USPP) in and around Washington, D. C. and through a suburban police department (MLMP), for the purpose of detecting illicit drug use. All blood samples were screened using an adapted Abuscreen RIA to non-urine (blood) procedure for the following drugs: THC, Cocaine, PCP, and Opiates. Forensic samples were confirmed through GC/MS. Results and characteristics of drug offenders are presented. It was found that 39 percent of sampled offenders from the MLMP showed measurable levels of cannabinoids. 9.5 percent of sampled offenders from the USPP showed measurable levels of Phencyclidine. Recommendations are made for the processing of suspected drug impaired drivers.
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PMID:The drug impaired driver. Detection and forensic specimen analysis. 158 Oct 24

Phencyclidine (PCP) has been found to affect neuroendocrine function by altering the release of the anterior pituitary hormones, adrenocorticotrophin, luteinizing hormone and prolactin. The purpose of this study was to examine the effect of PCP on release of the two pituitary hormones also derived from the adrenocorticotropin precursor, namely, alpha-melanocyte-stimulating hormone and beta-endorphin (beta-E), synthesized in the neurointermediate and anterior lobes of the pituitary. At behaviorally active doses, PCP administered i.c.v. increased plasma levels of immunoreactive beta-E (i beta-E) without affecting the concentration of immunoreactive alpha-melanocyte-stimulating hormone, suggesting that PCP increased the release of beta-E from only the anterior lobe of the pituitary. Dexamethasone pretreatment blocked the PCP-induced increase in i beta-E which indicated further the anterior lobe effects of PCP. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate), a selective PCP ligand, at behaviorally active doses also increased the plasma concentration of i beta-E. The dose-response curves for induction of behavior was very different from that for increasing the concentration of i beta-E in plasma. The increase in release of i beta-E was stereoselective as (+)-(1-(1-phenylcyclohexyl)-3 methylpiperidine but not (-)-(1-(1-phenylcyclohexyl)-3 methylpiperidine increased release of i beta-E. The increase in plasma levels of beta-E was not due to an interaction with opioid receptors because naloxone did not block PCP-induced release of beta-E. In vitro, PCP also significantly increased release of i beta-E from anterior lobe of the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phencyclidine increased release of beta-endorphin from anterior lobe of the pituitary. 165 42

Phencyclidine (PCP) receptors have been solubilized from rat forebrain membranes with the zwitterionic detergent 3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonate. Specific binding of the potent PCP receptor ligands [3H]thienyl-phencyclidine (TCP) and [3H]MK-801 was restored by incorporating extracted membrane protein into lipid vesicles prepared from a total brain lipid extract. A nearly quantitative recovery of solubilized receptor activity was achieved; this was dependent upon both the concentration of detergent used during membrane solubilization and the concentration of added lipid used during the reconstitution. The single, saturable, binding site measured for both [3H]TCP and [3H]MK-801 in solubilized and reconstituted preparations exhibited properties similar to those of the high affinity PCP binding site labeled by these ligands in brain membranes. The ability of ligands selective for this site (MK-801, TCP, and dexoxadrol) to competitively displace specific [3H]TCP binding was retained after solubilization and reconstitution, although IC50 values measured for these ligands were shifted to higher concentrations. Levoxadrol and haloperidol were ineffective at displacing the radioligand binding in both membrane and vesicle preparations. The additive and dose-dependent ability of glutamate and glycine to enhance [3H]TCP binding to the solubilized/reconstituted receptor further suggests that a direct interaction with the N-methyl-D-aspartate receptor/ion channel complex has been preserved in the vesicle preparations. The photoaffinity labeling of two polypeptides (Mr 98,000 and 59,000) by azido-[3H]PCP was demonstrated in the vesicle preparations; this was largely prevented by competitive displacement of the radioligand with PCP before photolysis. These results establish both an essential lipid dependency and polypeptide composition for the high affinity, haloperidol-insensitive, PCP receptor in brain.
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PMID:High efficiency reconstitution of a phencyclidine/MK-801 receptor binding site solubilized from rat forebrain membranes. 165 3

It is no longer tenable to attribute all the antipsychotic action of antipsychotic drugs to dopamine (DA) D2 receptor blockade and subsequent development of depolarization inactivation of the mesolimbic or mesocortical DA neurons. The chief evidence for this position is that clozapine (CLOZ) does not differ from typical antipsychotic drugs in these regards but is more effective than typical neuroleptic drugs. The mechanism of action of atypical antipsychotic drugs related to CLOZ may involve reduction of dopaminergic activity in the mesolimbic system by a variety of mechanisms, including D1 and D2 receptor blockade. Relatively higher affinity for the serotonin (5HT)2 receptor than for the D2 receptor may also be important to the action of CLOZ-like compounds. Enhanced DA release in the mesocortical system may be relevant to the effectiveness of these agents in treating negative symptoms. Several other classes of new agents alter the dopaminergic system by means of alternative mechanisms. Partial DA agonists may modulate DA neurotransmission more adequately than pure antagonists by producing a mix of direct agonist and antagonistic effects. DA autoreceptor agonists and 5HT3 antagonists appear to act by diminishing the release of DA from some, but not all, DA neurons. Substituted benzamides are "pure" D2 antagonists with some in vivo selectivity for limbic D2 over striatal D2 receptors. Highly selective D1 antagonists have been proposed to produce equivalent antipsychotic activity and fewer extrapyramidal symptoms than D2 antagonists. Antagonists of the recently identified D3 receptors are being sought. Excessive stimulation of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, leading to neurotoxicity or diminished activation of this receptor, is the target of novel approaches to treating schizophrenia. Phencyclidine (PCP) antagonists that would activate the NMDA receptor and sigma receptor antagonists are of interest as antipsychotic agents. Therapeutic strategies for treating schizophrenia, schizophrenia-related disorders, and other psychoses will likely be genuinely diverse in the next decade.
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PMID:The mechanism of action of novel antipsychotic drugs. 167 53

Phencyclidine (PCP) and sigma ligands produce a typical excitatory behaviour in rats, characterized by circling and head- and body-weaving. Excitatory amino acid antagonists such as 2-amino 5-phosphonovaleric acid (AP5) or 3-(+/-)-2-carboxypiperazin-4-yl)propyl-l-phosphonic acid (CPP) also produce a PCP-like excitatory behaviour in rats. In the present paper, the interactions between PCP/sigma drugs or excitatory amino acid receptor antagonists and haloperidol have been investigated in rats. In addition, the influence of two other butyrophenones having a different affinity for the sigma/haloperidol receptors, such as spiperone and 3-(4-(3(4-fluorobenzoyl)-propyl-piperazino-l-yl-isoquinolino (HR 375), has been tested on the behavioural and EEG effects of PCP/sigma drugs and excitatory amino acid antagonists. PCP (2.5-5 mg/kg IP), (+) or (-) SKF 10,047 (1-15 mg/kg IP), (+) or (-) cyclazocine (2-8 mg/kg IP) and AP5 (0.5 mumol ICV) dose-dependently and significantly (P less than 0.01) antagonized the haloperidol-induced catalepsy in the horizontal bar and podium tests in rats. On the other hand, either haloperidol (1 mg/kg IP) or spiperone (1 mg/kg IP) reduced the head-weaving induced by (+) SKF 10,047, PCP, or AP5. On the contrary, HR 375 (6 mg/kg IP) was ineffective in blocking the excitatory effects of these drugs. In addition, either haloperidol (1 mg/kg IP) or spiperone (1 mg/kg IP), but not HR 375 (6 mg/kg IP) reduced the amplitude increase of the fast (20-30 Hz) frequency/low (30-50 microV) voltage background cortical activity elicited by PCP or (+) SKF 10,047. The results demonstrate an interaction between dopamine and excitatory amino acid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Behavioural and electoencephalographic interactions between haloperidol and PCP/sigma ligands in the rat. 168 50

1. Phencyclidine (PCP) was incubated with rabbit liver and brain microsomal fractions, and the structures of metabolites formed by oxidation determined by g.l.c.-mass spectrometry. 2. The formation of several known mono- and di-hydroxylated metabolites, as well as two new metabolites, was seen in the liver preparations. 3. Hydroxylated PCP metabolites were also formed after incubation of PCP with brain microsomes, indicating that PCP biotransformation may occur in the brain itself.
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PMID:Identification of novel phencyclidine metabolites formed in vitro by rabbit microsomal metabolism. 176 23

Phencyclidine (PCP) (0.01-50 mumol.L-1) and its analogue, TCP (0.01-50 mumol.L-1) exhibited positive inotropic effects on electrically stimulated rabbit papillary muscle preparations. Dextrorphan (5 or 10 mumol.L-1) antagonized the actions of PCP in non-competitive manner (pD'2 = 5.25). This demonstrated the involvement of PCP receptors in the positive inotropic effects of PCP. By using high performance liquid chromatography with electrochemical detector (HPLC-ECD), an increase of DOPAC content was found in bath medium after PCP addition. Each of the dopamine receptor antagonists SCH23390, haloperidol and sulpiride (1 mumol.L-1) attenuated the maximal inotropic effects of PCP. These results suggest that PCP induces positive inotropic effects by increasing the release and/or blocking the uptake of dopamine.
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PMID:Effects of phencyclidine on contractile forces of isolated rabbit papillary muscles. 177 76


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