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)

Tri-, tetra- and pentachlorophenol (TCP, TeCP and PCP) can be considered the precursors in the formation of corresponding chloroanisoles, known to be powerful odorants in corks and wine. Determining the presence of these chlorophenolic compounds in cork soaking solutions (ethanol/water mixtures, 12% (v/v) ethanol used for cork quality control testing), or in wine can be achieved by acetylation/gas chromatography electron-capture detection. In order to reach the required sensitivity, a previous preconcentration step is necessary. Solid-phase extraction (SPE) and headspace solid-phase microextraction (HS-SPME) have given good results for the preconcentration of TCP, TeCP and PCP in such matrices. The use of Oasis HLB cartridges gives acceptable recoveries for the three compounds when different volumes (50-250 mL) of cork macerate with concentrations ranging from 20 to 150 ng/L are processed. Preconcentration based on HS-SPME has also been optimised with a 100 microm polydimethylsiloxane fibre and in situ derivatization. The HS-SPME method allows chlorophenols in a cork soaking solution and in wine to be determined with a limit of detection of 1 ng/L for each compound (in cork macerate) and a repeatability of around 0.5%-5% (n=8) for a concentration level of 30 ng/L.
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PMID:Development of solid-phase extraction and solid-phase microextraction methods for the determination of chlorophenols in cork macerate and wine samples. 1548 56

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

Permeable spheroplasts were prepared from two strains of Saccharomyces cerevisiae by incubating with zymolyase without a permeabilizing agent. The loss of the plasma membrane barrier was confirmed by the nucleotide release, the activity of glucose 6-phosphate dehydrogenase with external substrates and by the effects on respiration of mitochondrial substrates and ADP. Mitochondrial integrity was maintained, as shown by respiration with lactate, pyruvate, glucose and ethanol, and its acceleration by ADP showed a coupled respiration. Potassium uptake into the vacuole was measured with a selective electrode and found to be taken up effectively by spheroplasts only in the presence of Mg-ATP; it was reverted by CCCP and PCP and inhibited by bafilomycin A1, but not by sodium vanadate or sodium azide. Potassium ions did not alter DeltaPsi of the vacuole, followed with oxonol V, but caused vacuolar alkalinization, as followed with pyranine. The increase of vacuolar pH was non-selective and observed at 50-200 mM of several monovalent cations. Isolated vacuoles with pyranine inside showed similar changes of the internal pH in the presence of KCl. Results indicate that some strains do not require a permeabilizing agent to directly access the vacuole in spheroplasts prepared with zymolyase. The hypothesis about the existence of a K+/H+ antiporter in the vacuolar membrane of S. cerevisiae is discussed.
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PMID:In situ study of K+ transport into the vacuole of Saccharomyces cerevisiae. 1603 2

Ketamine is a dissociative anaesthetic that is being used in non-medical contexts. The effects of ketamine are very similar to those of phencyclidine, another dissociative anaesthetic that has enjoyed considerable popularity as a recreational drug. The effects of ketamine include analgesia, cardiovascular and respiratory stimulation, dissociation, hallucinations and anaesthesia. The potential dangers of uncontrolled ketamine use include psychosis and violence, accidents and marked psychomotor and cognitive impairment. Although studies have shown potential for tolerance to and physical dependence on ketamine, further investigation of these phenomena is needed. Ketamine is thought to produce most of its effects through antagonist activity at the PCP site of the NMDA receptor complex. Ketamine has sympathomimetic properties resulting from enhancement of catecholamine, and particularly dopamine, activity. While opioid receptor activity has been identified, this is relatively weak and the contribution to the effects of ketamine is not clear. Although much is known of the clinical uses and effects of ketamine, as yet little is understood of ketamine as a recreational drug and potential drug of dependence.
Drug Alcohol Rev 1996 Jun
PMID:Pharmacological properties of ketamine. 1620 65

Drugs of abuse share the ability to enhance dopaminergic neurotransmission in the dorsal and ventral striatum. The action of dopamine is modulated by additional neurotransmitters, including glutamate, serotonin and adenosine. All these neurotransmitters regulate the phosphorylation state of Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32). Phosphorylation at Thr(34) by protein kinase A converts DARPP-32 into a potent inhibitor of the multifunctional serine/threonine protein phosphatase, PP-1. Phosphorylation at Thr(75) by Cdk5 converts DARPP-32 into an inhibitor of protein kinase A. The state of phosphorylation of DARPP-32 at Thr(34) also depends on the phosphorylation state of Ser(97) and Ser(130), which are phosphorylated by CK2 and CK1, respectively. By virtue of regulation of these 4 phosphorylation sites, and through its ability to modulate the activity of PP-1 and protein kinase A, DARPP-32 plays a key role in integrating a variety of biochemical, electrophysiological, and behavioral responses controlled by dopamine and other neurotransmitters. Importantly, there is now a large body of evidence that supports a key role for DARPP-32-dependent signaling in mediating the actions of multiple drugs of abuse including cocaine, amphetamine, nicotine, caffeine, LSD, PCP, ethanol and morphine.
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PMID:DARPP-32 mediates the actions of multiple drugs of abuse. 1635 15

This study, based upon epidemiological survey data from the United States (U.S.) National Household Surveys on Drug Abuse (NHSDA) from 2000 to 2001, presents new estimates for the risk of developing a hallucinogen dependence syndrome within 24 months after first use of any hallucinogen (median elapsed time approximately 12 months). Subgroup variations in risk of becoming hallucinogen dependent also are explored. Estimates are derived from the NHSDA representative samples of non-institutionalized U.S. residents ages 12 and older (n=114,241). A total of 2035 respondents had used hallucinogens for the first time within 24 months prior to assessment. An estimated 2-3% of these recent-onset hallucinogen users had become dependent on hallucinogens, according to the NHSDA DSM-IV computerized diagnostic algorithm. Controlling for sociodemographic and other drug use covariates, very early first use of hallucinogens (age 10-11 years) is associated with increased risk of hallucinogen dependence (p<0.01). Excess risk of developing hallucinogen dependence was found in association with recent-onset use of mescaline; excess risk also was found for recent-onset users of ecstasy and of PCP. This study's evidence is consistent with prior evidence on a tangible but quite infrequent dependence syndrome soon after the start of hallucinogen use; it offers leads that can be confirmed or disconfirmed in future investigations.
Drug Alcohol Depend 2007 Mar 16
PMID:Who is becoming hallucinogen dependent soon after hallucinogen use starts? 1698 12

Vitreous humor (VH) is routinely collected at autopsy for the testing of electrolytes and ethanol. In recent years drugs of abuse have been detected in this specimen. In this study the authors assayed 30 VH samples for phencyclidine (PCP) and 50 specimens for cannabinoids. Specimens were screened by immunoassay and then assayed for PCP by GC-FID and cannabinoids by GC/MS. Eighteen (60%) specimens screened positive for PCP using a cutoff of 25 ng/mL. Quantitative analysis showed PCP concentrations in VH that screened positive ranged 30-290 ng/mL. Corresponding blood concentrations were 50-600 ng/mL. VH PCP concentrations in the 12 cases which screened negative were 40-470 ng/mL. False negative results were probably due to matrix effects. All VH specimens screened for cannabinoids were negative. Ten negative screening specimens assayed by GC/MS yielded 1 11-nor-9-carboxy-delta-9-tetrahydrocannabinol positive result at 2 ng/mL. These data indicated that VH maybe a useful specimen for the detection of PCP but not for cannabinoids.
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PMID:Phencyclidine and cannabinoids in vitreous humor. 1829 95

Potent N-methyl-d-aspartate (NMDA) receptor antagonists decrease volitional consumption of ethanol by rats. This study examined the effects of memantine, a low-affinity, open channel NMDA antagonist, on volitional consumption of ethanol by alcohol-preferring rats and potential locomotor, sedative and hypothermic effects. Volitional consumption of ethanol in a 24-hr two-choice paradigm was determined for male Myers' high-ethanol-preferring (mHEP) rats. Effects of memantine (0.3, 1.0, 3.0 and 10.0 mg/kg, i.p., b.i.d. [twice daily] for 3 days) or vehicle on volitional consumption of ethanol, proportion of ethanol to total fluids consumed, total fluid intake and consumption of food were observed. Potential sedating and locomotor effects of memantine (10.0 mg/kg, i.p., b.i.d.) were determined using an elevated plus maze and an Auto-Track Opto-Varimex activity monitoring system. Rectal temperature was measured to determine if memantine (10.0 mg/kg, i.p.) produces a hypothermic effect. The results indicate that memantine dose-dependently decreased the amount of ethanol and proportion of ethanol to total fluids consumed daily, reaching 48% and 24%, respectively, at the highest dose. These effects did not appear to be anti-caloric. Memantine (10.0 mg/kg) partially reversed both the sedation and the reductions in locomotor activity induced by ethanol. This dose did, however, produce a small, partially reversible hypothermic effect. In conclusion, memantine may decrease ethanol consumption with fewer side effects than other NMDA receptor antagonists, such as phencyclidine (PCP), MK 801 and ketamine.
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PMID:Effects of the non-competitive NMDA receptor antagonist memantine on the volitional consumption of ethanol by alcohol-preferring rats. 2021 Jul 93

Executive dysfunction is a common symptom among alcohol-dependent individuals. Phencyclidine (PCP) injection induces dysfunction in the prefrontal cortex of animals but little is known about how PCP affects the response to ethanol. Using the in vivo microdialysis technique in male Wistar rats, we investigated how systemic injection of 5 mg/kg PCP would affect the dopamine release induced by local infusion of 300 mM ethanol into the nucleus accumbens. PCP given 60 min before ethanol entirely blocked ethanol-induced dopamine release. However, when ethanol was administered 60 min before PCP, both drugs induced dopamine release and PCP's effect was potentiated by ethanol (180% increase vs 150%). To test the role of prefrontal cortex dysfunction in ethanol reinforcement, animals were pretreated for 5 days with 2.58 mg/kg PCP according to previously used 'PFC hypofunction protocols'. This, however, did not change the relative response to PCP or ethanol compared to saline-treated controls. qPCR illustrated that this low PCP dose did not significantly change expression of glucose transporters Glut1 (SLC2A1) or Glut3 (SLC2A3), monocarboxylate transporter MCT2 (SLC16A7), glutamate transporters GLT-1 (SLC1A2) or GLAST (SLC1A3), the immediate early gene Arc (Arg3.1) or GABAergic neuron markers GAT-1 (SLC6A1) and parvalbumin. Therefore, we concluded that PCP at a dose of 2.58 mg/kg for 5 days did not induce hypofunction in Wistar rats. However, PCP and ethanol do have overlapping mechanisms of action and these drugs differentially affect mesolimbic dopaminergic transmission depending on the order of administration.
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PMID:Ethanol and phencyclidine interact with respect to nucleus accumbens dopamine release: differential effects of administration order and pretreatment protocol. 2058 92

Addictive drugs, such as opioids, ethanol, cocaine, amphetamine, and phencyclidine (PCP), affect many functions of the nervous system and peripheral organs, resulting in severe health problems. G protein-activated inwardly rectifying K(+) (GIRK, Kir3) channels play an important role in regulating neuronal excitability through activation of various Gi/o protein-coupled receptors including opioid and CB(1) cannabinoid receptors. Furthermore, the channels are directly activated by ethanol and inhibited by cocaine at toxic levels, but not affected by methylphenidate, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) at toxic levels. The primary pharmacological action of PCP is blockade of N-methyl-D-aspartate (NMDA) receptor channels that are associated with its psychotomimetic effects. PCP also interacts with several receptors and channels at relatively high concentrations. However, the molecular mechanisms underlying the various effects of PCP remain to be clarified. Here, we investigated the effects of PCP on GIRK channels using the Xenopus oocyte expression system. PCP weakly but significantly inhibited GIRK channels at micromolar concentrations, but not Kir1.1 and Kir2.1 channels. The PCP concentrations effective in inhibiting GIRK channels overlap clinically relevant brain concentrations in severe intoxication. The results suggest that partial inhibition of GIRK channels by PCP may contribute to some of the toxic effects after overdose.
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PMID:Inhibition of g protein-activated inwardly rectifying k channels by phencyclidine. 2188 98


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