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 in vitro metabolism of phencyclidine (PCP) was investigated in 9000 g supernatant fractions of both control and PCP-, ketamine-, ethanol-, phenobarbital- or isosafrole-pretreated rats. Levels of PCP, trans-4-phenyl-4-piperidinocyclohexanol (I), 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (II), N-(5-hydroxypentyl)-1-phenylcyclohexylamine (IX), and 5-(1-phenylcyclohexylamino)-valeric acid (X) were monitored by gas chromatographic analysis in all cases. The inhibition of metabolism by N2, CO, SKF-525A or 2,4-dichloro-6-phenylphenoxyethylamine (DPEA), or deletion of NADPH or protein, implied the involvement of cytochrome P-450 in the reactions. The various inducing agents affected the metabolism of PCP in different ways, implying that at least several isozymes of cytochrome P-450 were involved in the total metabolism. The majority of the consumed PCP was not accounted for by the measured metabolites so that some other metabolic pathways of major quantitative importance must be operative.
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PMID:Induction of phencyclidine metabolism by phencyclidine, ketamine, ethanol, phenobarbital and isosafrole. 670 76

Groups of rats, acclimated to drinking both water and 10% v/v ethanol were implanted with a variety of slow-release devices containing d-amphetamine (d-amp), nicotine, caffeine, phencyclidine (PCP), secobarbital, LSD, mescaline or haloperidol. Ethanol intake was elevated only during treatment with d-amp or nicotine; none of the other drugs affected ethanol consumption even though the amounts of all drugs released were pharmacologically sufficient to affect behavior. Nicotine treated rats were not simply seeking calories provided by the EtOH solution, since nicotine treatment did not enhance intake of a distinctively flavored solution isocaloric to 10% ethanol. These results support a self-medication model of ethanol intake.
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PMID:Ethanol intake increases during continuous administration of amphetamine and nicotine, but not several other drugs. 686 54

Disposition of [H] Phencyclidine in brain, plasma and adipose tissue of rats acutely and chronically-treated with ethanol was studied using a method possessing high sensitivity and specificity for PCP. In rats acutely-treated with ethanol (5 g/kg PO dose) and PCP (10 mg/kg IP dose), dispositional factors did not play a role in the intensifies pharmacological and behavioral effects of PCP. However in rats chronically-treated with 2.5 g/kg PO dose of ethanol twice a day for 19 days, the disposition of PCP (5 mg/kg IP dose) was significantly altered and the values of PCP in brain, plasma and adipose tissue were significantly higher than those in the control group. Although inhibition of PCP metabolism and a comparatively slower rate of its elimination appear to account for the potentiation of drug effects in animals chronically-treated with ethanol, interaction of drugs at the level of the central nervous system cannot be ruled out.
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PMID:Effect of acute and chronic ethanol pre-treatment on the disposition of phencyclidine (PCP) in the rat. 708 42

Five street samples of leafy material coated with phencyclidine (PCP) were analyzed by a gas chromatographic nitrogen detection assay. The samples contained 15.6+1.8% PCP by weight or 32.2+ 13.8 mg PCP per "joint". An aliquot of a joint was smoked with a laboratory apparatus and the vaporized PCP was collected on a filter. Only 22.6+8.0% of the PCP or 6.7+2.1 mg PCP, reached the filter. This amount is in an approximation of the dose of PCP which becomes available to the oral and pulmonary mucosa following the smoking of a single PCP coated joint.
Subst Alcohol Actions Misuse 1982
PMID:Estimation of phencyclidine in leafy mixtures and in vapor phase after smoking. 713 55

A pharmacokinetic analysis comparing a 2 and 3 compartment model was performed on the published data of Wall et al. (12) on the kinetics of phencyclidine (PCP). These investigators gave 100 micrograms (mean 1.3 micrograms/kg) of 3H-PCP i.v. to three human volunteers and followed the plasma disappearance of PCP over 72 hr. They suggested that PCP followed a 2 compartment model with a plasma half life of 7-16 hr. In the present analysis, additional pharmacokinetic estimations from the plasma data were made and a 3 compartment model developed. The results obtained suggest complex PCP kinetics involving an initial pi half life of 5.5 min, an alpha half life of 4.6 hr, and a beta half life of 22 hr. The volume of distribution was large, varying from 2.2 to 2.4 1/kg for each compartment, suggesting binding of PCP.
Subst Alcohol Actions Misuse 1982
PMID:Comparison of two and three compartment models of phencyclidine in man. 716 62

An analysis of 68 phencyclidine (PCP) users who sought treatment reveals that chronic compulsive, daily use occurs and that intravenous use is relatively common. Twenty-five (37%) subjects considered themselves to be addicted to PCP and 19 (29%) desired medication to assist withdrawal. Unwanted behaviors under the influence of PCP were common and primarily related to memory loss, or acts which resulted from loss of impulse control.
Drug Alcohol Depend 1981 Nov
PMID:Characteristics of 68 chronic phencyclidine abusers who sought treatment. 732 87

We investigated the effect of ethanol on specific binding of [3H]MK-801 to the intrachannel phencyclidine (PCP) receptor site, as an index of change in the functional response of the N-methyl-D-Aspartate (NMDA)-associated ion channel. Saturation binding experiments were performed on synaptic membrane homogenates from adult rat cortex and hippocampus. [3H]MK-801 binding assays were conducted under conditions of basal, 10 microM glutamate, or 10 microM glutamate + 30 microM D-serine, with and without 50 or 100 mM ethanol. Association experiments of [3H]MK-801 binding (5 nM) were conducted under conditions of 0 or 10 microM glutamate, with varying concentrations of glycine (0.01, 0.10, and 10 microM) with and without 100 mM ethanol. Ethanol (50 and 100 mM) significantly decreased the percentage of high-affinity (open-channel state) MK-801 receptors with a concomitant increase in percentage of low-affinity receptors, but did not change high- and low-affinity constants of the two binding states. An ethanol-induced increase in the closed-channel receptor density in basal and activated conditions was suggested by the saturation experiments. Association experiments further explained this finding, in that ethanol (100 mM) significantly decreased fast component (open-channel) [3H]MK-801 binding in conditions of glycine (0.01-10 microM) only and activated conditions of glutamate + glycine (0.01-0.10 microM). However, the observed fast and slow kinetic rate constants of [3h]MK-801 binding, as well as total specific binding (fast + slow components), were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
Alcohol Clin Exp Res 1995 Apr
PMID:Alteration of [3H]MK-801 binding associated with the N-methyl-D-Aspartate receptor complex by acute ethanol in rat cortex and hippocampus in vitro. 762 62

Diagnostic concordance of DSM-III, DSM-IV and ICD-10 was tested in a heterogeneous unrestricted sample of 370 clinical cases drawn from a regional consortium. Agreement for abuse/harmful use, dependence, and the collapsed category of 'any diagnosis' was studied across eight drug classes. A probabilistic approach to the cross-classifications based on configural frequency analysis was applied, permitting the computation of four indices of agreement. In contrast to earlier studies, ICD-10 appeared to be the most inclusive system, and often diagnosed cases that were undiagnosed by both DSMs. Generally satisfactory coherence between the ICD-10 harmful use category and the DSM category of abuse was found, but this agreement was often due to a preponderance of negative or undiagnosed cases; disagreement was common on which cases in particular warrant a mild diagnosis. In general, the greatest diagnostic concordance was observed for sedative/hypnotics, opiates and alcohol, the poorest for amphetamines, cocaine and PCP. The analytic approach produced an array of cross-system relationships that are more complex and conditional than those previously reported, and scientists and clinicians are cautioned to study particular drugs, diagnostic levels and measures of concordance before applying cross-system results to their own data or design needs.
Drug Alcohol Depend 1994 Dec
PMID:Diagnostic concordance of substance use disorders in DSM-III, DSM-IV and ICD-10. 788 10

Two studies examined the abuse potential of the N-methyl-D-aspartate (NMDA) non-competitive antagonist eliprodil [(+/-)-alpha-(4-chlorophenyl)-4-[(fluorophenyl)methyl]-1- piperidineethanol] by evaluating its reinforcing effects in rhesus monkeys and its phencyclidine (PCP)-like discriminative stimulus effects in rats. The monkeys were trained to self-administer PCP i.v. under a fixed ratio 10 schedule of reinforcement. After the monkeys were trained, saline, vehicle and various doses of eliprodil were substituted for PCP. The rats were trained to discriminate 3 micrograms/kg PCP from saline using a standard two-lever discrimination procedure with correct-lever responding reinforced under a fixed ratio 10 schedule of food reinforcement. After acquiring the discrimination, the rats were tested with various doses of PCP, dizocilpine and eliprodil. The self-administration study showed that eliprodil did not have reinforcing effects, since it maintained injection rates comparable to the negative controls, saline and vehicle. In the discrimination study it was found that the higher doses of PCP and dizocilpine resulted in 100% PCP-associated lever responding, whereas eliprodil occasioned no responding on the PCP-associated lever. The results from these studies suggest that eliprodil has a low potential for abuse in humans as well as providing further evidence that eliprodil produces a profile of behavioral effects unlike the PCP-site selective NMDA antagonists.
Drug Alcohol Depend 1994 Jun
PMID:Evaluation of the reinforcing effects of eliprodil in rhesus monkeys and its discriminative stimulus effects in rats. 795 50

Rats were trained to discriminate a dose of 1.75 mg/kg phencyclidine (PCP) from saline. During substitution tests, both PCP (0.3-10.0 mg/kg) and the non-competitive NMDA antagonist, MK-801 (0.01-0.3 mg/kg) substituted for the PCP stimulus in a dose-dependent manner. In contrast, delta 9-tetrahydrocannabinol (delta 9-THC, 0.1-5.6 mg/kg) and delta 8-tetrahydrocannabinol (delta 8-THC, 0.3-5.6 mg/kg) failed to substitute for the PCP stimulus, up to doses that substantially decreased rate of responding. However, both delta 9-THC and delta 8-THC partially attenuated the discriminative stimulus effects of the PCP training dose. Furthermore, a dose of 3.0 mg/kg delta 9-THC shifted the PCP dose-effect curve for discriminative stimulus effects to the right and shifted the PCP dose-effect curve for rate of responding to the left. The attenuation of the PCP stimulus by delta 9-THC lacked a strong dose-dependent relationship and was observed both at doses which did not alter rate of responding, as well as at doses which substantially decreased rate. In contrast to the effects observed with delta 9-THC and delta 8-THC, morphine, d-amphetamine and chlordiazepoxide failed to attenuate the discriminative stimulus effects of PCP, even at doses that markedly decreased rate of responding. The present findings suggest that delta 9-THC and delta 8-THC alter the discriminative stimulus effects of PCP in a pharmacologically specific manner.
Drug Alcohol Depend 1994 Apr
PMID:Discriminative stimulus effects of phencyclidine: pharmacologically specific interactions with delta 9- and delta 8-tetrahydrocannabinol. 805 36


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