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)

In 15 patients hospitalized with phencyclidine (PCP) psychosis, several measures of psychopathology were examined in relationship to urine PCP levels, duration of hospitalization and mode of intoxication. Duration of hospitalization was found to be significantly shorter for smokers than for ingesters of PCP. Impaired ability to estimate 30 seconds duration was found to correlate significantly with a higher urine PCP level and a longer hospitalization. No other measure of psychopathology was found to correlate with either duration of hospitalization or urine PCP levels, now were other measures of psychopathology found to distinguish these patients from patients with acute functional mental illness.
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PMID:Acute phencyclidine (PCP) intoxication: psychopathology and prognosis. 68 4

Both stimulant-induced and phencyclidine (PCP)-induced psychoses have been proposed as models of the idiopathic psychosis of schizopherenia. In this two-part study, the phenomenology of the psychosis associated with a period of cocaine intoxication was evaluated retrospectively in 34 male crack cocaine-dependent patients without concomitant psychiatric disorder and then was compared with the psychosis of 16 actively psychotic schizophrenic men (without a history of drug or alcohol abuse in the past year). Certain First Rank Schneiderian Symptoms (FRSS) were more commonly observed in the schizophrenic patients (e.g., thought broadcasting, thought withdrawal) than in the cocaine addicts. In the second part of this study, we retrospectively examined the cocaine and PCP experiences of an additional 22 cocaine addicts who had a past history of separate periods of cocaine and PCP use. Overall, the frequency of FRSS recalled during periods of cocaine and PCP intoxication was similar. However, the psychosis related to cocaine intoxication was more associated with an intense suspiciousness and paranoia related to a fear of being discovered or harmed while using cocaine. PCP-induced psychosis was less associated with suspiciousness and more associated with delusions of physical power, altered sensations, and unusual experiences [e.g., out of body experiences, experiencing religious figures or events directly (e.g., being with Noah at the time of the Arc)]. As elements of both cocaine and PCP psychosis can be found in schizophrenia, a model integrating the mechanisms of several psychotogenic drugs may be more informative. Such an integrative model might better capture the heterogeneity of psychotic symptoms that can be seen in schizophrenia. Furthermore, different pharmacologic interventions (e.g., "anti-stimulant" versus "anti-PCP") might address different aspects of the positive symptom picture in schizophrenia.
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PMID:Phenomenologic comparison of the idiopathic psychosis of schizophrenia and drug-induced cocaine and phencyclidine psychoses: a retrospective study. 931 84

The aims of the present study were to evaluate the extent to which primary care physicians' (PCPs) identification of psychiatric distress is related to a number of nonpsychopathological factors, such as patient sociodemographic and health-related characteristics, and to assess the impact of depression on PCP identification of psychiatric distress, controlling for patient sociodemographic and health-related characteristics. Two patient samples were chosen to explore these issues: 1) patients not fulfilling any ICD-10-defined or subthreshold psychiatric diagnosis and, 2) patients with an ICD-10 diagnosis of current depression. Patients attending 46 primary care clinics during an index period were screened by the General Health Questionnaire (GHQ)-12 and selected for a second stage interview according to GHQ score. Among the 559 interviewed patients, 123 had no mental disorder and 66 had an ICD-10 current depressive disorder. Identification of psychiatric distress by the PCP was associated with retirement among subjects without mental disorders but not among depressed patients. Patient's negative overall health self-perception and severity of physical illness were significantly related to identification of psychiatric distress in the two groups, whereas neither disability nor reason for medical consultation had a significant effect. Patients with current depression, compared with those without, were 4.3 times more likely to be identified by PCPs as having psychiatric distress when adjusting for all the above nonpsychopathological variables. Patients with depression and comorbid anxiety disorders were more likely to be recognized by the PCP as compared with those with pure depression. Finally, among depressive symptoms, diurnal variation and symptoms related to suicidal tendencies were predictive of identification of psychiatric distress, whereas increase of appetite was negatively associated with PCP recognition.
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PMID:Identification of psychiatric distress by primary care physicians. 943 85

The prevalence of psychiatric disorders was examined in a sample of 204 pretrial jail detainees receiving standard drug treatment. More than half of the sample had at least one lifetime DSM-III-R axis I diagnosis, and the lifetime rates of serious mental illness were higher than reported prevalence rates for arrestees in general jail populations. Detainees with comorbid disorders were more likely than others to have more than one co-occurring psychiatric disorder, to have been arrested for property crimes, and to be dependent on alcohol, marijuana, or PCP. The findings argue for the expansion of integrated treatment services within criminal justice drug treatment settings.
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PMID:Psychiatric illness and comorbidity among adult male jail detainees in drug treatment. 1057 85

The phencyclidine (PCP) model of schizophrenia suggests that N-methyl-D-aspartate (NMDA) receptor hypofunction and its consequences may play an important role in the pathophysiology of this psychiatric disorder. Moreover, the schizophreniform psychosis caused by PCP resembles schizophrenia in all of the relevant domains of psychopathology, especially negative symptoms and cognitive dysfunction. Because of interest in the PCP model and possible NMDA receptor hypofunction in schizophrenia, animal behaviors elicited by PCP and its analogues have been characterized. These preclinical models may serve to identify candidate compounds that possess therapeutic efficacy in schizophrenia. Ideally, negative symptoms and cognitive dysfunction would also serve as therapeutic targets for these novel medications. In the current study, the ability of topiramate to attenuate the severity of a specific behavior elicited by MK-801 (dizocilpine), a high affinity analogue of PCP was studied in mice. Topiramate was chosen because it addresses two of the predicted pathological consequences of NMDA receptor hypofunction. Specifically, topiramate potentiates GABAergic neurotransmission and antagonizes the excitotoxic actions of glutamate at the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate (KA) classes of glutamate-gated channels. Topiramate was shown to inhibit MK-801-elicited "popping" behavior in a complex dose-dependent manner.
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PMID:Topiramate antagonizes MK-801 in an animal model of schizophrenia. 1216 15

Schizophrenia is a debilitating chronic psychiatric illness affecting 1% of the population. The cardinal features of schizophrenia are positive symptoms (thought disorder, hallucinations, catatonic behavior), negative symptoms (social withdrawal, anhedonia, apathy) and cognitive impairment. Although progress in elucidating the aetiology of schizophrenia has been slow, new insights on the neurochemical and neurophysiological mechanisms underlying the pathophysiology of this illness are beginning to emerge. The glutamate/N-methyl-D-aspartate (NMDA) hypofunction hypothesis of schizophrenia is supported by observations that administration of NMDA glutamate receptor antagonists such as phencyclidine (PCP) or ketamine induces psychosis in humans; moreover, decreased levels of glutamate and changes in several markers of glutamatergic function occur in schizophrenic brain. Administration of PCP or ketamine to rodents elicits an increase in locomotion and stereotypy accompanied by an increase in glutamate efflux in several brain regions. Systemic administration of group II metabotropic glutamate (mGlu) receptor agonists suppresses PCP-induced behavioral effects and the increase in glutamate efflux. Activation of group II mGlu receptors (mGlu2 and mGlu3) decreases glutamate release from presynaptic nerve terminals, suggesting that group II mGlu receptor agonists may be beneficial in the treatment of schizophrenia. In addition, pharmacological manipulations that enhance NMDA function may be efficacious antipsychotics. Selective activation of mGlu5 receptors significantly potentiates NMDA-induced responses, supporting this novel approach for the treatment of schizophrenia. The glutamate hypothesis of schizophrenia predicts that agents that restore the balance in glutamatergic neurotransmission will ameliorate the symptomatology associated with this illness. Development of potent, efficacious, systemically active drugs will help to address the antipsychotic potential of these novel therapeutics. This review will discuss recent progress in elucidating the pharmacology and function of group II mGlu and mGlu5 receptors in the context of current hypotheses on the pathophysiology of schizophrenia and the need for new and better antipsychotics.
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PMID:Metabotropic glutamate receptors: potential drug targets for the treatment of schizophrenia. 1276 19

Delirium is thought to be a temporary psychiatric disorder resulting from a reduced central cholinergic transmission, combined with an increased dopaminergic transmission. The cholinergic and the dopaminergic systems interact not only with each other but with glutamatergic and gamma-amino-butyric acid (GABA) pathways. Besides the cerebral cortex, critical anatomical substrates of psychosis pathophysiology would comprise the striatum, the substantia nigra/ventral tegmental area, and the thalamus. The thalamus acts as a filter, allowing only the relevant information to travel to the cortex. Drugs of abuse (e.g. PCP, Ecstasy), as well as psychoactive medications frequently prescribed to hospitalized patients (e.g. benzodiazepines, opioids) could compromise the thalamic gating function, leading to sensory overload and hyperarousal. We propose that drug-induced delirium would result from the transient thalamic dysfunction caused by exposure to medications that interfere with central glutamatergic, GABAergic, dopaminergic and cholinergic pathways at critical sites of action. This model provides directions for future studies in neurophysiology, in vivo brain imaging, and psychopharmacology investigating delirium neuropathophysiology.
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PMID:Psychotogenic drugs and delirium pathogenesis: the central role of the thalamus. 1561 51

Schizophrenia is one of the most important forms of psychiatric illness and may be chronic and highly disabling. It has been suggested that specific neurochemical abnormality is due to dopaminergic overactivity in the brain. Schizophrenia is currently thought to be associated with a hypoglutamatergic state that is mimicked by acute Phencyclidine (PCP), an antagonist of the N-methyl-D-aspartate (NMDA) receptor subtype. Administration of PCP or ketamine in rodents has been used to model aspects of schizophrenia. Taken into consideration the role of glutamatergic system in development of schizophrenia and involvement of striatal dopaminergic receptors in generation of schizophrenia symptoms, it was planned to study functional interaction between NMDA and metabotropic glutamatergic receptors 5 (mGluR5) in schizophrenia-associated behavioral and memory disturbance and the role of mGluRs allosteric modulation in cortico-striatal synaptic plasticity. In our experiments investigation of dose-dependent effects of ketamine revealed that 0.3mg/kg ketamine induces statistical changes most of behavioral and cognitive parameters in rats. Changes in emotional state showed decrease of the number and total duration of groomings in open field experiments as wall as in passive avoidance task. Decrease of motor activity was also detected, while no significant changes were observed in number of defecations. In T-maze test it was shown that spatial memory was damaged. To determine whether mGlu5 and NMDA receptor interact to regulate complex behaviors that are relevant to cognitive disorders such as schizophrenia we focused on assessing whether the selective mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine MPEP mimics or exacerbates the effects of the NMDA receptor antagonist. Ketamine-induced memory disturbance was significantly increased after injection of mGluR5 negative allosteric modulators MPEP. In In vitro experiments the agonist at group I metabotropic glutamate receptors (mGluRI) (RS)-3,5-dihydroxyphenyl-glycine (DHPG,100 microM) evoked a persistent depression of the second component (N2) of the cortico-striatal field potential in rat slices. DHPG-induced plasticity was not NMDA-dependent. mGlu5 negative allosteric modulator MPEP diminishes the inhibition of synaptic responses induced by DHPG and completely blocked the late phase of depression. Our behavioral and in vitro data suggested that between NMDA and mGlu5 receptors there are functional interaction. Thus in some neurological or psychiatric disorders with NMDA dysfunction pharmacological manipulation of mGlu5 receptors could have therapeutic use.
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PMID:The role of the mGluR allosteric modulation in the NMDA-hypofunction model of schizophrenia. 2009 Jan 56

Schizophrenia is a complex and devastating mental disorder of unknown etiology. Hypofunction of N-methyl-D-aspartate (NMDA) receptors are implicated in the disorder, since phencyclidine (PCP) and other NMDA receptor antagonists mimic schizophrenia-like symptoms in humans and animals so well. Moreover, genetic linkage and post mortem studies strongly suggest a role for altered neuregulin 1 (Nrg1)/erbB4 signaling in schizophrenia pathology. This study investigated the relationship between the NMDA receptor and Nrg1 signaling pathways using the perinatal PCP animal model. Rats (n=5/group) were treated with PCP (10 mg/kg) or saline on postnatal days (PN) 7, 9 and 11 and were sacrificed on PN12, 5 weeks and 20 weeks for biochemical analyses. Western blotting was used to determine total and phosphorylated levels of proteins involved in NMDA receptor/Nrg1 signaling in the prefrontal cortex and hippocampus. In the cortex, PCP treatment altered Nrg1/erbB4 expression levels throughout development, including decreased Nrg1 and erbB4 at PN12 (-25-30%; p<0.05); increased erbB4 and p-erbB4 (+18-27%; p<0.01) at 5 weeks; and decreased erbB4 and p-erbB4 (-16-18%; p<0.05) along with increased Nrg1 (+33%; p<0.01) at 20 weeks. In the hippocampus, levels of Nrg1/erbB4 were largely unaffected apart from a significant decrease in p-erbB4 at 20 weeks (-13%; p<0.001); however NMDA receptor subunits and PSD-95 showed increases at PN12 and 5 weeks (+20-32%; p<0.05), and decreases at 20 weeks (-22-29%; p<0.05). This study shows that NMDA receptor antagonism early in development can have long term effects on Nrg1/erbB4 expression which could be important in understanding pathological processes which might be involved in schizophrenia.
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PMID:Perinatal phencyclidine treatment alters neuregulin 1/erbB4 expression and activation in later life. 2196 13

Subchronic treatment with the N-methyl-d-aspartate receptor antagonist phencyclidine (PCP) is a valuable approach to model the symptomatology of schizophrenia, a multi-facetted psychiatric disorder, in rodents. We addressed the question whether subchronic PCP (scPCP) treatment (5 mg/kg bidaily for 7 days) would affect anxiety in rats, since contradictory findings have been reported so far. Anxiety-like behaviour was assessed using the light-enhanced startle paradigm (LES), a method which measures the effect of the natural aversion to light on the startle reflex and does not depend on motivated behaviour or exploratory drive. For comparison, anxiety-like behaviour was measured in the light-dark exploration test (LDT) and in an open field environment (OFT). The scPCP-treatment did not affect baseline startle reactivity or light-enhanced startle, suggesting normal anxiety levels in treated animals. Further, normal anxiety-like behaviour was also found in the OFT. In the LDT, scPCP treated rats displayed shorter latencies to enter the lit compartment and shuttled more between the dark and lit compartments, behaviours indicative of decreased anxiety and/or increased exploratory activity. Our findings therefore suggest that the effects of scPCP-treatment on anxiety-like behaviour are task-dependent and recommend the additional use of tests independent from exploratory drive or other motivated behaviours, such as the LES paradigm.
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PMID:Differential effects of subchronic phencyclidine on anxiety in the light-enhanced startle-, light/dark exploration- and open field tests. 2329 39


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