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)

Drugs such as phencyclidine (PCP) that interact with PCP and sigma binding sites can produce psychotomimetic effects that resemble some symptoms of schizophrenia. Therefore, it has been suggested that PCP and sigma receptors may be important in the clinical manifestations of schizophrenia. Assays of these two binding sites in human postmortem brains showed consistent significant reductions in the density of sigma, but not PCP sites, in schizophrenics as compared with age-matched and postmortem interval-matched normal and suicide controls. Reductions in the density of sigma binding sites in schizophrenia were most prominent in temporal cerebral cortex, and were accompanied by a small increase in affinity for the ligand [3H]haloperidol. These data provide the first evidence for alterations in sigma binding sites in schizophrenia, and suggest that selective sigma ligands may be useful in the treatment of the disorder.
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PMID:Selective loss of cerebral cortical sigma, but not PCP binding sites in schizophrenia. 184 13

PCP is metabolized extensively in the body via a variety of metabolic routes. Biotransformation is a major mechanism of PCP elimination in humans and termination of PCP action in mice. In general, PCP metabolites are less active pharmacologically than PCP itself. Primary metabolism involves hydroxylation of the alicyclic rings at several carbon atoms by cytochrome P-450-mediated monooxygenase. Hydroxylation of the aromatic ring seems to be less likely and has not been conclusively demonstrated. Hydroxylation of PCP at carbon 2 of the piperidine ring to form the unstable carbinolamine leads to formation of a series of polar, open-ring compounds. Monohydroxylated metabolites are conjugated with glucuronic or sulfuric acid, or are further hydroxylated to dihydroxy derivatives that can also be subject to conjugation. Formation of highly reactive electrophilic metabolites of PCP have been demonstrated in vitro in microsomal preparations. Covalent modification of tissue macromolecules by reactive intermediates can be responsible for suicide inactivation of cytochrome P-450 and can possibly mediate some long-term toxic effects of PCP. PCP inhaled by cigarette smoking is metabolized via similar routes. About 50% of the PCP in cigarette smoke is converted to PC, a major product of thermal degradation of PCP. PC and its hydroxylated and conjugated metabolites appear to contribute little to the pharmacology or acute toxicity of PCP.
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PMID:Biotransformation of phencyclidine. 391 38

Snowball sampling techniques were used to generate a sample of 200 phencyclidine users from an area with a 10-year history of extensive PCP use. Three types of users were studied: heavy chronic, light chronic, and recreational users. The extent of PCP use varied from less than twice a month for a period of 6 months to daily use for several consecutive years. Each subject participated in a structured interview which lasted an average of 11/2 h. Subjects were asked about the acute effects of PCP, and about their moods before, during, and after using PCP. Scales based on previous research were used to measure the acute effects and moods. Results showed that heavy chronic users were more likely than recreational users to feel energized by PCP, and to experience negative ideations (thoughts about suicide and death). When age was controlled for, heavy chronic users were also more likely to experience violent effects. Analysis of moods over time showed some similar patterns between heavy chronic and recreational users, as well as some striking differences. Overall, heavy chronic users reported greater mood elevations while high on PCP, and a more dramatic drop in mood after the high wore off, than recreational users. Analysis of the results by user types clarified some of the confusion about contradictory descriptions of the effects of PCP, and point to the need to continue distinguishing between user types.
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PMID:Acute effects of phencyclidine (PCP) on chronic and recreational users. 730 11

Isolated pancreatic islets from rats and humans express a plasmalogen-preferring ATP-stimulatable, Ca(2+)-independent phospholipase A2 (ASCI-PLA2) enzyme which participates in the glucose-stimulated hydrolysis of arachidonate from membrane phospholipids and in insulin secretion. Here we report that clonal insulin-secreting HIT beta-cells contain substantial amounts of endogenous plasmalogens and express a similar ASCI-PLA2 activity with the following properties: (1) Enzymatic activity as well as glucose-induced eicosanoid release and insulin secretion are inhibited by a mechanism-based suicide substrate directed towards ASCI-PLA2. (2) HIT cell ASCI-PLA2 is selectively activated and protected against thermal denaturation by ATP. (3) The magnitude of ASCI-PLA2 activation by the nonhydrolyzable ATP analog AMP-PCP is similar to that by ATP. (4) The ATP concentrations required to activate ASCI-PLA2 fall within physiologic ranges in the presence of Mg2+. (5) ADP induces a concentration-dependent attenuation of the activation of ASCI-PLA2 by ATP. HIT cell ASCI-PLA2 exhibited an apparent isoelectric point of 7.5 on chromatofocusing analysis and was quantitatively adsorbed to an ATP-agarose matrix and selectively desorbed from this column by ATP. Mono-Q anion-exchange analysis of the active ATP-agarose eluant yielded a peak of ASCI-PLA2 activity associated with a single protein band with an apparent molecular mass of 40 kDa. Similar chromatographic behavior of the rat pancreatic islet ASCI-PLA2 activity was observed during sequential ATP-agarose and Mono-Q anion-exchange steps. These results indicate that HIT cells express an ASCI-PLA2 similar to the analogous islet enzyme and suggest that expression of this enzyme and of its preferred plasmalogen substrates may be a general property of insulin-secreting beta-cells.
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PMID:Characterization of an ATP-stimulatable Ca(2+)-independent phospholipase A2 from clonal insulin-secreting HIT cells and rat pancreatic islets: a possible molecular component of the beta-cell fuel sensor. 800 9

This study presents self-report cross-sectional and longitudinal data on associations between drug use, suicide ideation, and attempts in a multiethnic sample of seventh- and eighth-grade male adolescents attending school in the greater Miami, Florida, area. African Americans had the highest prevalence of 6-month ideation (20.5%), and Haitians had the highest attempts (11.4%). For the total sample, tranquilizers had the highest odds ratio for ideation (3.4), and PCP for attempts (6.2). Psychoactive drug-use was consistently related to attempts among Hispanics, white non-Hispanics, and African Americans. Acculturation strains interacted with cocaine and crack to predict suicide attempts among Hispanic respondents.
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PMID:The relationship of drug use to suicide ideation and attempts among African American, Hispanic, and white non-Hispanic male adolescents. 834 10

Predictors of non-response were investigated in a 15-year follow-up (1981-1996) of 3,481 individuals in a probability sample from the household population of East Baltimore. Demographics (age, sex, race, education, marital status, and unemployment), household factors (living arrangements, household income, household size, and number of children), cultural variables (ancestral ethnicity and foreign language), social variables (social support and networks, committing felony, carrying a weapon, using an alias, and wandering), health factors (physical illness, health insurance, medical assistance, Medicare, receiving disability benefits, social security, and welfare), interviewer's observation, and psychopathologic variables (mental disorders, suicide behavior, comorbidity, and drug use) were collected at baseline in 1981 and in 1982, then linked to follow-up data between 1993 and 1996. A tracing process involving mail, phone, criss-cross directories, motor vehicle administration records, a commercial credit bureau, the state criminal justice system, hospital records, the US National Death Index, and field tracing were used to locate the original sample. A total of 3,066 respondents of the original sample (88.1%) were traced. Non-response was categorized into Sample Mortality (that part of the original sample that died during follow-up), Sample Loss (that part of the original sample that survived but could not be found) and Refusal (that part of the original sample that survived and was found but refused to participate). Stratified analysis and adjusted multiple logistic regression modeling found sample mortality and sample loss were strongly influenced by individual and household variables and by psychopathology. Sample mortality was influenced by specific mental disorders or conditions as mania, drug abuse/dependency, antisocial personality, cognitive impairment, alcohol abuse/dependency, phobia, drug use (except PCP), and comorbidity. Household factors protective against mortality include higher household income, not living as extended members in a married couple family, and living with children in the household. Persons who were unemployed, widowed or single, without high school education, male, and 65 years of age or older were more likely to die. Sample loss was influenced by cognitive impairment, antisocial personality, and cocaine use. Household factors linked to sample loss include living in female-headed families, or non-family households, and living alone. Young nonwhite, divorced/separated, without high school education, and unemployed were also harder to find. Refusal was associated with being white, with incomplete elementary education, living as a spouse in traditional married couple families, or as a child in female-headed families. Psychopathology did not influence refusal.
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PMID:Psychopathology and attrition in the Baltimore ECA 15-year follow-up 1981-1996. 1018 15

Here, I will review accumulating evidence that during the developmental period of synaptogenesis, also known as the brain growth spurt period, neurons are very sensitive to specific disturbances in their synaptic environment. During this period, abnormal increases in NMDA glutamate (Glu) receptor activity triggers excitotoxic neurodegeneration, and abnormal inhibition of neuronal activity (by blockade of NMDA Glu receptors or excessive activation of GABAA receptors) triggers neuronal suicide (apoptosis). Only a transient disturbance, lasting for a few hours, is sufficient to trigger either excitotoxic or apoptotic neurodegeneration during this developmental period. Ethanol, which has both NMDA antagonist and GABAmimetic properties, triggers widespread apoptotic neurodegeneration in the developing rat, mouse or guinea pig brain, and this provides a likely explanation for the reduced brain mass and lifelong neurobehavioral disturbances associated with the human fetal alcohol syndrome (FAS). The brain growth spurt occurs in different species at different times relative to birth. In rats and mice it is a postnatal event, but in humans it extends from the 6th month of gestation to several years after birth. Thus, there is a period in fetal and neonatal human development, lasting for several years, during which immature central nervous system (CNS) neurons are exquisitely sensitive to environmental agents (the specific number and variety of which remains to be established) that can trigger widespread neurodegeneration by inducing specific abnormal changes in the synaptic environment. Agents identified thus far include drugs that may be abused by pregnant mothers (ethanol, phencyclidine (PCP) (angel dust), ketamine (Special K), nitrous oxide (laughing gas), barbiturates, benzodiazepines) and many medicinals used in obstetric and pediatric medicine as sedatives, anti-convulsants or anesthetics (all general anesthetics are either NMDA antagonists or GABAmimetics). Many other chemicals in the human environment remain to be evaluated for their ability to cause developing CNS neurons to commit suicide, and this provides an exciting challenge for the field of developmental neurotoxicology.
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PMID:New insights and new issues in developmental neurotoxicology. 1252 Jul 55

Methoxydine is a dissociative anaesthetic belonging to the arylcyclohexylamine class. This substance shows pharmacodynamic similarities with ketamine, a medication with demonstrated rapid-acting antidepressant effects. Like ketamine, results of binding assays have shown that methoxydine is an uncompetitive antagonist of NMDA receptor approximately as potent as ketamine, but less potent than PCP. Furthermore, unlike ketamine, it acts as a dopamine, serotonin, and noradrenaline reuptake inhibitor as well as an agonist at sigma-1, sigma-2, and opioid receptors. The hypothesis is that methoxydine can produce rapid antidepressant effects in depressed patients with high risk of suicide, including depressed alcoholics.
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PMID:Is methoxydine a new rapid acting antidepressant for the treatment of depression in alcoholics? 2360 63

The aim of the study was to explore differences and similarities between the various non-natural manners of death (accident, suicide, homicide) regarding toxicological findings in illicit drug users. Medicolegal autopsy reports from the Institute of Forensic Medicine University of Oslo concerning deaths from 2000 to 2009 were investigated. Those aged 20-59 whose manner of death was non-natural and who tested positive for any narcotic drug (morphine/heroin, amphetamines, ecstasy, cannabis, LSD, PCP, and high levels of GHB in addition to methadone and buprenorphine) were selected. All substance findings were registered and categorized (narcotics, ethanol, and medicinal products). Of the 1603 autopsies that met the selection criteria, 1204 were accidental intoxications, 122 accidents other than intoxication, 114 suicides by intoxication, 119 non-intoxication suicides, and 44 victims of homicide. Poly drug use was found in all manners of death. The drug profile as well as the mean number of substances (illicit drugs and medicinal products) varied from 2.9 to 4.6 substances per case, depending on the manner of death. Intoxication suicides had the highest number of substances and a total drug profile similar to accidental intoxications. Non-intoxication suicides had a total drug profile similar to homicide and accidents other than intoxication. The number of substances found per case increased during the decade, mainly due to increased findings of methadone, cannabis, amphetamines, and benzodiazepines. Methadone findings increased much more than buprenorphine. Methadone was found 20 times more often than buprenorphine in accidental intoxication cases. In summary, poly drug findings are common in adults who suffer a non-natural death while using illicit drugs. The different manners of death have some specific characteristics and significant differences regarding drug profile.
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PMID:Non-natural manners of death among users of illicit drugs: Substance findings. 2463 34

A 30-year-old male patient developed a hallucinogen persisting perception disorder (HPPD) after smoking cannabis laced with phencyclidine (PCP) or lysergic acid diethylamide (LSD) 10 years prior to hospital admission. Clinically, he reported seeing vivid, saturated colors and caricature-like objects. The patient described perceiving objects or people in motion as moving faster than normal. He reported living in a dream-like state and feeling numb and detached from other people and his surroundings. Upon pharmacotherapy initiation, facility transfer, and subsequent discharge from an acute psychiatry unit, he ultimately committed suicide. Although hallucinogen abuse is common in the United States, this case suggests that HPPD maybe significantly underdiagnosed and undertreated. In some cases, this oversight may perpetuate years of unnecessary patient suffering and can ultimately lead to severe depression and suicide.
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PMID:Hallucinogen Persisting Perception Disorder and Risk of Suicide. 2563 75


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