Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of phencyclidine (PCP) on regional cerebral glucose utilization was determined by using quantitative autoradiography with [14C]-2-deoxyglucose. PCP increased brain metabolism in selected areas of cortex, particularly limbic, and in the basal ganglia and thalamus, whereas the drug decreased metabolism in areas related to audition. These results are consistent with the known physiology of central PCP neurons and may help to suggest brain areas involved in PCP-mediated actions. Moreover, based on the behavioral similarities between PCP psychosis and an acute schizophrenic episode, these data may be relevant to the understanding of schizophrenia. The PCP-receptor-acylating agent, metaphit, blocked most of these PCP actions. In addition, metaphit by itself was found to diminish glucose utilization rather uniformly throughout brain. These results indicate an antagonist effect of metaphit on the PCP system and suggest a widespread action of metaphit, putatively at a PCP-related site, possibly in connection with the N-methyl-D-aspartate (NMDA) receptor.
 ...
PMID:PCP-induced alterations in cerebral glucose utilization in rat brain: blockade by metaphit, a PCP-receptor-acylating agent. 285 Jun 26

Multiple studies have reported about substance abuse in Blacks and Hispanics. However, little is known about substance-abusing psychiatric patients of these ethnic groups. This study reports the prevalence and patterns of substance abuse among 171 consecutive patients (90 Blacks and 81 Hispanics) admitted to the acute psychiatric unit of an inner-city general hospital. The lifetime prevalence was 63%. Within the month prior to admission, 48% had used the following substances: cannabis, 40%; alcohol, 37%; amphetamines, 20%; cocaine, 12%; phencyclidine (PCP), 12%; barbiturates and/or sedative-hypnotics, 10%; opioids, 9%; inhalants, 1%; hallucinogens, 1%. Those who abused alcohol were more likely to abuse barbiturates and/or sedative-hypnotics, and opioids. Logistic regression analysis showed that major depression, ethnicity, and schizophrenia each were significant predictors of particular types of abuse. Patients with major depression were less likely to use PCP, Blacks were more likely than Hispanics to use hallucinogens, and schizophrenics were less likely to use opioids. In all cases in which sex, age, and personality disorder were significant, males, the young adult group, and those with personality disorder were more likely to be abusers. These three variables were all strong predictors of both multiple and extensive substance abuse. Overall, our findings suggest that in the inner-city, a substantial number of young adult psychiatric inpatients are a high risk group for multiple substance abuse. The coexistence of substance abuse and other psychiatric disorders has clinical and treatment implications, and calls attention for changes within the conventional psychiatric milieu.
 ...
PMID:Inner-city substance abuse patterns: a study of psychiatric inpatients. 326 29

Based on commonalities between peripheral blood "immunocytes" and central nervous system cells (both have receptors for endorphins, enkephalins, dopamine, acetylcholine, etc.) blocking of potassium ion channels in both brain cell synaptosome and suppressor T cells, and common sharing of antigenic determinants on one or another immunocyte and one or another CNS cells, we postulated that peripheral blood immunocytes can be used to study CNS mechanisms. In the present studies we used peripheral blood lymphocytes to study the effects of phencyclidine (PCP) on various receptors. This agent causes a permanent psychosis similar to chronic schizophrenia in a small percent of users. We observed similar effects in binding to sigma receptors, inhibition of binding and reversibility of binding in receptors of both human peripheral blood receptors and the mouse neuroblastoma, a hamster brain cell hybrid clone. The results are complete with the hypothesis that some cases of schizophrenia are immunologically mediated, perhaps due to antibodies to the sigma receptor. Alternatively, immunologic deficiency might hinder elimination of neurotropic viruses which in genetically predisposed individuals bind to and block the sigma receptor. Functional deficiency of the brain cell equivalent of lymphocyte suppressor T cells by one or another immunologic mechanisms or an excess of T helper cells might also cause schizophrenia by causing an excess of normal brain "B-cell equivalent cell" output response to sensory input.
 ...
PMID:Sigma receptors and autoimmune mechanisms in schizophrenia: preliminary findings and hypotheses. 609 18

Phencyclidine (1-(1-phenylcyclohexyl)piperidine [PCP]), a behaviorally active analogue (1-(1-m-aminophenylcyclohexyl)piperidine [m-amino-PCP]), and two behaviorally inactive analogues (1-(1-m-nitrophenylcyclohexyl)piperidine and 1-piperidinocyclohexanecarbonitrile) block neuromuscular transmission, depress the amplitude and rate of rise of directly elicited action potentials in frog sartorius muscle, and cause voltage- and concentration-dependent decreases of the peak end-plate current amplitude. This implies that all four compounds block the ion channel of the acetylcholine (ACh) receptors. Only PCP and m-amino-PCP prolong the action potential, block delayed rectification, potentiate muscle twitch, increase quantal content of end-plate potentials, and block K+-induced 86Rb+ efflux from rat brain synaptosomes. PCP also possesses central and peripheral antimuscarinic activity but is much less potent than 3-quinuclidinyl benzilate (QNB). Atropine, scopolamine, and QNB require much higher concentrations to induce behavioral alterations than to block muscarinic receptors. Thus PCP and some of its behaviorally active and inactive derivatives share two common effects, blockade of the nicotinic ACh receptor-ion channel complex and blockade of central and peripheral muscarinic receptors. The feature that apparently separates behaviorally active from inactive derivatives of PCP is their ability to block K+ conductance (gK) and thereby potentiate muscle twitch and increase the release of transmitters from central and peripheral synapses. The similarity between PCP-induced behavioral alterations and primary schizophrenia in humans raises the possibility of involvement of an altered gK in the human disease.
 ...
PMID:Interactions of phencyclidine with ion channels of nerve and muscle: behavioral implications. 630 62

Phencyclidine [1-(phenylcyclohexyl)piperidine; PCP], in low dose (approximately equal to 0.1-0.2 mg/kg of body weight), induces a schizophrenia-like behavioral syndrome in man; this effect has been attributed to block of neuronal K channels. We used a K-stimulated 86Rb efflux assay to demonstrate that low concentrations of PCP (10-50 nM) block a class of depolarization-activated K channels in rat brain synaptosomes--pinched-off presynaptic nerve terminals. The dose-response curve is biphasic, and much higher PCP concentrations (greater than 10 microM) are required to block the remainder of the K-stimulated 86Rb efflux. The [3H]PCP binding curve for synaptosomes is also biphasic: PCP binds to some components with high affinity (Kd approximately equal to 6.0 X 10(-8) M), and to other components with much lower affinity (Kd approximately equal to 1.15 X 10(4) M). PCP can be photoactivated with UV light to form covalent bonds: after UV irradiation, previously-bound [3H]PCP is no longer displaceable by a large excess of unlabeled PCP. Preliminary data from NaDodSO4/polyacrylamide gel electrophoresis studies after covalent binding of [3H]PCP to synaptosomes, suggest that the high-affinity binding site may be on a large protein (Mr approximately equal to 220,000). We conclude that the high-affinity PCP binding protein is associated with the K channels that are blocked by nanomolar concentrations of PCP. Block of these channels could, by prolonging action-potential duration in presynaptic nerve terminals, enhance calcium entry and neurotransmitter release, thereby altering transmission at central synapses involved in behavioral expression.
 ...
PMID:Phencyclidine in nanomolar concentrations binds to synaptosomes and blocks certain potassium channels. 630 43

A previously healthy 33-year-old patient developed a schizophrenia-like psychosis of 5 weeks' duration after inhalation of hashish contaminated with phencyclidine (PCP). The literature is reviewed and the epidemiology, clinical features, therapy and neuropharmacology of phencyclidine intoxication are discussed.
 ...
PMID:[Phencyclidine (PCP): a psychotomimetic drug. Case report and review of literature]. 663 38

Phencyclidine (PCP), a widely abused drug currently, has multiple pharmacological actions, including psychotomimetic [1], anesthetic [2], sympathomimetic [2], anticholinergic [3-7], and dopaminergic [8-10]. Similarly, PCP intoxication in man can present with diverse symptoms: schizophrenia-like delusions and hallucinations; mania; violence, dyskinetic, catatonic, or stereotyped movements; hypertension; and coma [11, 12]. There is general agreement that the treatment of PCP intoxication includes support of vital functions and acidification of the urine [13]. However, there is no known specific antidote for PCP toxicity. Although diazepam [13], haloperidol [14, 15], and chlorpromazine [16] have been reported to improve the agitation and psychotic symptoms caused by PCP, the therapeutic efficacy of these agents has rarely been documented with objective clinical measures. Recently we found that intramuscular physostigmine and haloperidol [17, 18] improved several symptoms of acute PCP intoxication as measured by the Brief Psychiatric Rating Scale (BPRS) [19].
 ...
PMID:Phencyclidine intoxication: assessment of possible antidotes. 713 17

Routine blood samples of 145 consecutive patients seen in the Los Angeles County Psychiatric Hospital Emergency Room during a 48-hour weekday period in June 1979 were examined for phencyclidine (PCP) using a sensitive and specific gas capillary gas chromatographic nitrogen detector (GC2-N) method. Of these 145 samples 63 (43.4%) were positive and PCP levels ranged 0.34 to 142.9 nanograms/ml (mean 14.6 ng/ml +/- 3.4 S.E.M.). An analysis of the records of these 63 patients revealed a wide variety of psychotic clinical pictures resembling mania, depression or schizophrenia with relatively few of the supposedly characteristic manifestations of PCP intoxication. Each of the 63 patients had at least one manifestation of toxic psychosis and/or acute delirium, in addition to the florid symptoms characteristic of functional states. PCP measurement, pharmacokinetics and the possible relationships of this intoxication to the psychiatric manifestations are discussed.
 ...
PMID:The urban epidemic of phencyclidine (PCP) use: clinical and laboratory evidence from a public psychiatric hospital emergency service. 721 23

Phencyclidine (PCP) is a dissociative anesthetic whose abuse is a growing problem. Historically, its effects have been considered remarkably like those of the schizophrenic state, but in vitro and in vivo neuropharmacologic data are somewhat inconsistent with the dopaminergic hypothesis of schizophrenia. The physiologic and psychiatric manifestations of PCP intoxication are diverse and somewhat dose dependent. Urine acidification may hasten drug excretion.
 ...
PMID:Phencyclidine intoxication: insights into a growing problem of drug abuse. 743

Antipsychotic agents were tested for their ability to antagonize both dopaminergic-induced and non-competitive N-methyl-D-aspartate (NMDA) antagonist-induced behaviors. All of the agents dose-dependently antagonized the apomorphine-induced climbing mouse assay (CMA) and dizocilpine (MK-801)-induced locomotion and falling assay (MK-801-LF) with a CMA/MK-801-LF ratio of less than or equal to 1.6. However, clozapine and its structural analog olanzapine more potently antagonized MK-801-LF (1.1 and 0.05 mg/kg) than the CMA (12.3 and 0.45 mg/kg) and as a result had a CMA/MK-801-LF ratio of 11.2 and 9, respectively. Furthermore, phencyclidine (PCP) (2 mg/kg) can selectively induce social withdrawal in naive rats that were housed in pairs (familiar) for 10 days prior to testing without affecting motor activity. SCH 23390, raclopride, haloperidol, chlorpromazine and risperidone failed to reverse the social withdrawal induced by PCP up to doses which produced significant motor impairment. However, clozapine (2.5 and 5.0 mg/kg) and olanzapine (0.25 and 0.5 mg/kg) significantly reversed this social withdrawal in rats. Therefore, the non-competitive NMDA antagonists PCP and MK-801 can induce behaviors in Rodents which are selectively antagonized by clozapine and olanzapine. Furthermore, assessment of the effects of antipsychotic agents in the CMA, MK-801-LF and PCP-induced social withdrawal assays may provide a preclinical approach to identify novel agents for negative symptoms and treatment resistant schizophrenia.
 ...
PMID:Antipsychotic agents antagonize non-competitive N-methyl-D-aspartate antagonist-induced behaviors. 748 May 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>