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 effects of delta 9-tetrahydrocannabinol (delta 9-THC) in combination with phencyclidine (PCP) or ethanol were examined in rats responding under a fixed-consecutive-number schedule of food presentation. Under this schedule, a minimum of 13 consecutive responses on one lever followed by one response on another lever produced food. When administered alone, PCP (0.1-10.0 mg/kg) and delta 9-THC (0.1-5.6 mg/kg), but not ethanol (0.3-1.7 g/kg), decreased accuracy. PCP, delta 9-THC, and ethanol alone all produced dose-dependent decreases in rate of responding. A dose-effect curve for PCP or ethanol was then redetermined in combination with selected doses of delta 9-THC (0.125-1.75 mg/kg) and the data were analyzed according to the effect-addition and dose-addition models of additivity. When administered in combination, delta 9-THC produced dose-dependent leftward shifts in the PCP dose-effect curves for both accuracy and rate of responding. The interactions for PCP + delta 9-THC combinations were effect-additive for accuracy. In contrast, the type of interaction obtained for PCP + delta 9-THC combinations on rate of responding depended upon the particular doses combined, as well as on the model used to analyze the interactions. According to the effect-addition model, these interactions were additive at low doses of delta 9-THC and supraadditive at the highest dose. However, according to the dose-addition model the interactions at the higher doses of delta 9-THC were infraadditive. Delta 9-THC also shifted the ethanol dose-effect curve for rate of responding to the left but did not alter the ethanol dose-effect curve for accuracy. The interactions for ethanol + delta 9-THC combinations were effect-additive for accuracy and both effect- and dose-additive for rate of responding. The present investigation clearly illustrates the importance of examining an extensive range of dose combinations on different behavioral measures, as well as the use of appropriate analyses in studies designed to evaluate the interactions between drugs.
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PMID:Delta 9-tetrahydrocannabinol interactions with phencyclidine and ethanol: effects on accuracy and rate of responding. 132 18

Analytical methods developed for the Finnigan MAT ITS40 gas chromatograph-ion trap mass spectrometer (GC/MS) were evaluated for the confirmation of drugs-of-abuse in urine. The specific drugs evaluated are those listed by the National Institute on Drug Abuse (NIDA): 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (9-carboxy-THC), benzoylecgonine (BE), codeine and morphine, phencyclidine (PCP), amphetamine, and methamphetamine. Drugs were extracted from urine using solid-phase columns, separated by capillary gas chromatography, and analyzed by ion trap mass spectrometry following electron impact ionization. All drugs except PCP were derivatized prior to analysis. The full scan limits of detection (LOD), quantitation (LOQ), and linearity were 2.5, 5.0, and 1000 ng/mL, respectively, for 9-carboxy-THC; 37, 75, and 5000 ng/mL for BE; 50, 100, and 2500 ng/mL for the opiates; 0.25, 0.50, and 500 ng/mL for PCP; and 50, 100, and 5000 ng/mL for the amphetamines. The limits of detection (LOD) and limits of quantitation (LOQ) met the minimum criteria for the signal-to-noise (S/N) ratio and spectral match criteria for drug identification. Absolute LODs and LOQs (in ng/mL) for the ITS40 based on single ion monitoring of blank urines were: 0.8 and 2.0 for 9-carboxy-THC; 8.9 and 25 for BE; 3.3 and 9.6 for codeine; 6.2 and 16.7 for morphine; 0.25 and 0.32 for PCP; 0.7 and 2.0 for amphetamine; and 2.4 and 5.7, for methamphetamine, respectively. The coefficient of variation ranged from 5 to 10%, and analytical recoveries were in the range of 90-114%. The ion trap mass spectrometer permits full scan identification of drugs while maintaining analytical LOQ that are below NIDA guidelines, and has equivalent or better detection limits to quadrupole analyzers for high sensitivity applications.
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PMID:Evaluation of full-scanning GC/ion trap MS analysis of NIDA drugs-of-abuse urine testing in urine. 152 18

A three-way crossover study was performed to determine the influence of delta 9-tetrahydrocannabinol (THC) and ethanol (EtOH) separately upon phencyclidine (PCP) disposition in dogs. Seven dogs were given three single dose treatments: 1.5 mg PCP kg-1 i.v., 1.5 mg PCP kg-1 i.v. with 0.4 mg kg-1 THC i.v., and 1.5 mg PCP kg-1 i.v. with 1.25 g EtOH kg-1 i.v. PCP was measured in plasma samples collected for 24 h after administration of each treatment, with several pharmacokinetic parameters calculated from the plasma concentration vs time data. The PCP serum Cls values were significant change in V beta or t1/2. EtOH did not induce significant changes in any PCP pharmacokinetic parameter, although mean Cls and V beta were increased. These results confirm the observed THC inhibition of PCP metabolism, and suggest that the enhanced pharmacologic action of PCP by THC may result from higher serum PCP concentrations. These results further suggest that enhanced PCP actions by acute EtOH administration may result from increased PCP distribution to the CNS.
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PMID:Effects of ethanol and delta 9-tetrahydrocannabinol on phencyclidine disposition in dogs. 164 25

The ability to alter immunoassay test results by the addition of some commonly available chemicals to drug-positive and drug-negative urine specimens was investigated. Urine specimens containing either phencyclidine (PCP) or 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (9-THC-COOH) were adulterated with sodium chloride, bleach, vinegar, potassium hydroxide, liquid soap, 2-propanol, and ammonia. Subsequent analyses by radioimmunoassay (RIA) and fluorescence polarization immunoassay (FPIA) demonstrated false positive and false negative results with some adulterants. Radioimmunoassay false positives occurred with potassium hydroxide (PCP and THC-COOH assays) and bleach (THC-COOH assay) adulterants. Bleach (PCP assay) and soap (THC-COOH assay) additives resulted in false negative analyses by RIA. No adulterant caused FPIA false positives. FPIA false negatives occurred with bleach (PCP and THC-COOH assays) and potassium hydroxide (PCP assay) adulterants.
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PMID:Detectability of phencyclidine and 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in adulterated urine by radioimmunoassay and fluorescence polarization immunoassay. 196 89

To drug-free urine specimens, we added the following drugs of abuse to give concentrations twice the cutoff value for positive test results: 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (9-carboxy-THC), oxazepam, secobarbital, morphine, benzoylecgonine, amphetamine, or phencyclidine (PCP). Visine was then added. Although measured concentrations of several drugs were decreased in the presence of Visine, false-negative results were obtained only for 9-carboxy-THC for the EMIT-d.a.u. and TDx urine cannabinoid assays. Visine also decreased 9-carboxy-THC as measured by the Abuscreen assay. At low concentrations of Visine, false-negative cannabinoid results were attributable to the benzalkonium chloride ingredient of Visine. The added Visine was not detectable by routine urine analysis and had no effect on the activity of the glucose-6-phosphate dehydrogenase-drug conjugate used in the EMIT-d.a.u. assays. Moreover, analysis by gas chromatography/mass spectrometry showed no chemical modification or loss of 9-carboxy-THC in the Visine-adulterated urine specimens. However, Visine did increase the adhesion of 9-carboxy-THC to the borosilicate glass specimen containers. Results of ultrafiltration studies with Visine suggest that 9-carboxy-THC partitions between the aqueous solvent and the hydrophobic interior of benzalkonium chloride micelles, thereby reducing the availability of 9-carboxy-THC in antibody-based assays.
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PMID:Mechanism of false-negative urine cannabinoid immunoassay screens by Visine eyedrops. 246 64

In this study, the combined effects of chronic phencyclidine (PCP) and delta 9-tetrahydrocannabinol on spermatogenesis in mice were examined. Mice were treated with THC (50 mg/kg, PO) and PCP (15 mg/kg, IP) alone or in combination for 16 days and with PCP alone for 35 days. THC had a significant effect on spermatogenesis and decreased the number of all germinal cells. PCP, on the other hand, affected all germinal cells except spermatids after 35 days of treatment. Combination of THC and PCP treatment caused a significant decrease in resting and pachytene spermatocytes. Similarly, combination of these two drugs caused a significant increase in cauda epididymal abnormal sperms. These results suggest that THC and PCP may cause greater disruption in spermatogenesis when they are abused together.
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PMID:Interactive effects of chronic phencyclidine and delta 9-tetrahydrocannabinol on spermatogenesis in mice. 255 53

Water-deprived rats were given daily opportunities (2.0-hr sessions) to take water or a sweet solution (20% or 24% sugar-water). After stable intakes of each fluid were achieved, the effects of phencyclidine hydrochloride (PCP), delta-9-tetrahydrocannabinol (THC), ethanol (E), and morphine (M) on intakes were tested. PCP, THC, and M all enhanced intake of the sweet solution, while E produced varying effects across doses tested. With other rats, nearly the same procedure was used except that the test solution presented with water was 0.9% sodium chloride. Doses of PCP enhanced intake of the salty solution. These data, combined with the data from similar studies of the effects of opioids and benzodiazepines, indicate that a wide variety of agents that are self-administered also modify intake of ingesta.
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PMID:PCP, THC, ethanol, and morphine and consumption of palatable solutions. 285 70

The behavioral and pharmacological interactions between delta 9-tetrahydrocannabinol (delta 9-THC) and phencyclidine (PCP) were studied following coadministration of the drugs in smoke to mice. While delta 9-THC (25, 50 or 100 mg/cigarette) had little effect on spontaneous motor activity, all doses attenuated the hyperactivity elicited by PCP X HCl (25 and 50 mg/cigarette). delta 9-THC produced a dose-related hypothermia. PCP X HCl (50 mg/cigarette) had no effect on body temperature but enhanced hypothermia when combined with 25 mg of delta 9-THC. delta 9-THC (100 mg/cigarette) had no effect on the biodisposition of 3H-PCP and its pyrolytic product, 3H-phenylcyclohexene (3H-PC), when examined immediately after 3H-PCP X HCl (50 mg/ cigarette) exposure. At 30 min, brain, liver, lung and plasma contained higher concentrations of 3H-PC and fat and plasma contained lower concentrations of 3H-PCP in the mice exposed to both drugs compared to 3H-PCP X HCl alone. It appears, therefore, that delta 9-THC has the potential for altering the behavioral, pharmacological and pharmacokinetic sequelae of PCP abuse.
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PMID:Interactions between phencyclidine and delta 9-tetrahydrocannabinol in mice following smoke exposure. 629 42

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.
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PMID:Discriminative stimulus effects of phencyclidine: pharmacologically specific interactions with delta 9- and delta 8-tetrahydrocannabinol. 805 36

A simple and rapid screening procedure with Triage has been developed to detect 7 classes of drugs of abuse, phencyclidine (PCP), benzodiazepines (BZO), cocaine metabolite (COC), amphetamines (AMP), cannabinoids (THC), opiates (OPI), and barbiturates (BAR), in hemolyzed blood. A clear supernatant was obtained by mixing the blood with sulfosalicylic acid. The supernatant was neutralized with ammonium acetate and then screened using Triage. The lower limits of detection of the Triage screening method for PCP, diazepam, benzolyecgonine, methamphetamine, morphine, 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), phenobarbital, and secobarbital were 50 ng/mL, 900 ng/mL, 1,000 ng/mL, 600 ng/mL, 900 ng/mL, and 900 ng/mL, respectively. The sensitivity of Triage for THC-COOH in deproteinized blood samples was much lower than that in urine samples. No false positive reactions were observed for the 6 classes of the drugs of abuse with the exception of AMP when the blood was decomposed. Phenethylamine, a putrefactive amine, gave positive results for AMP at concentrations over 5,000 ng/mL. The method was applied to 9 hemolyzed blood samples and 3 turbid urine samples from 12 forensic autopsy cases suspected of drug misuse. Among these, 5 were positive for AMP, 1 for OPI, and 4 for BAR. The presence of methamphetamine is only one of the 5, codeine in 1, and phenobarbital in 4 was confirmed by gas chromatography. All 4 samples which were false positive for AMP contained phenethylamine at relatively high concentrations because of moderate to heavy putrefaction. This method, although disadvantageous to test for AMP and THC, is helpful for the forensic toxicologist because any kind of bloody fluid can be tested rapidly with Triage to detect toxic levels of PCP, BZO, COC, OPI, and BAR.
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PMID:Application of the Triage panel for drugs of abuse to forensic blood samples. 869 49


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