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

In this study, we investigated whether risperidone, a serotonin-S2A (5-HT2A)/dopamine-D2 (D2)-receptor antagonist, inhibits phencyclidine (PCP)-induced stereotyped behaviors in comparison with haloperidol and ritanserin. Moreover, we also attempted to investigate the effects of these antipsychotics on the contents of dopamine, serotonin (5-HT) and their metabolites in rat striatum and frontal cortex. In rats, PCP (5 mg/kg, i.p.) caused hyperlocomotion and stereotyped behaviors, including sniffing, head-weaving, backpedalling and turning. Both resperidone (0.8-2.4 mg/kg, p.o.) and haloperidol (0.3-1.0 mg/kg, p.o.) inhibited these behaviors, except for backpedalling, in a dose-dependent manner. PCP (10 mg/kg, i.p.) produced hyperlocomotion and stereotyped behaviors, including rearing, sniffing head-twitch, backpedalling and turning. Risperidone (0.8-2.4 mg/kg, p.o.) inhibited both hyperlocomotion and PCP-induced behaviors, except for backpedalling, while ritanserin (3-10 mg/kg, p.o.) inhibited only the head-twitch. These results suggest that risperidone may have an antipsychotic effect on schizophrenia as well as PCP psychosis in humans by exerting a mixed 5-HT2A/D2 antagonism. Neurochemically, the increasing effects of risperidone on the content of DOPAC and the ratio of DOPAC to dopamine in the striatum were lower than those of haloperidol. These findings may support the view that the extrapyramidal side effects of risperidone are lower than those of haloperidol in clinical situations.
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PMID:Effects of risperidone on phencyclidine-induced behaviors: comparison with haloperidol and ritanserin. 753 32

Phencyclidine (PCP), in a dose of 15 mg/kg, produced delayed cognitive dysfunction (at 24 h) in rats subjected to water maze tasks. At 24 h after PCP administration, ataxia, hyperlocomotion and stereotyped behavior were not induced. NE-100, N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-enthylamine monohydrochloride, a selective and potent sigma receptor ligand, was administered orally 10 min after PCP administration or 15 min before the first trial (24 h after PCP administration). In both cases, NE-100 dose-dependently attenuated the delayed cognitive dysfunction induced by PCP. As these findings show that ingestion of PCP led to delayed cognitive dysfunction similar to the cognitive signs of psychosis seen in humans, NE-100 is being further studied for possible treatment of subjects with schizophrenia.
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PMID:Effect of NE-100, a novel sigma receptor ligand, on phencyclidine- induced delayed cognitive dysfunction in rats. 760 28

The effect of various typical (haloperidol) and atypical (clozapine, raclopride, remoxipride) antipsychotics on phencyclidine (PCP)-induced disruption of sensorimotor gating was tested in rats using an acoustic startle paradigm. Clozapine (4-40 mumol/kg), haloperidol (1-5 mumol/kg) and raclopride (1-12 mumol/kg) failed to reverse PCP-induced disruption of prepulse inhibition (PPI) of the acoustic startle response. In contrast, remoxipride (12-60 mumol/kg) caused a dose-dependent block of this effect. PCP-induced disruption of PPI is a widely accepted animal model of a corresponding behavioural deficit observed in schizophrenia although little evidence has been presented that it is in fact sensitive to antipsychotic agents. The present results indicate that remoxipride behaves in a unique way in this model compared to clozapine, haloperidol and raclopride.
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PMID:The atypical antipsychotic, remoxipride, blocks phencyclidine-induced disruption of prepulse inhibition in the rat. 770 Oct 46

1. Phencyclidine (PCP) reduces the latency of rats diving into a water-filled pool from a hidden platform, without stereotyped behavior. 2. The sigma-selective ligand, NE-100 (N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethyl-amine monohydrochloride), attenuates the effects of PCP in this procedure. 3. The serotonin2 (5-HT2) antagonist, ritanserin, and the sigma receptor ligands, 1-(cyclopropylmethyl)-4-[2'(4"-fluorophenyl)-2'-oxoethyl]- piperidine HBr (Dup734), 4-[2'-(4"-cyanophenyl)-2'-oxoethyl]-1- (cyclopropylmethyl)piperidine (XJ448), alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY14802) and rimcazole similarly attenuate the effects of PCP. 4. The dopamine D2/sigma ligands, haloperidol and cis-N-(1-benzyl-2-methyl-pyrrolidin-3-yl)-2-methoxy-5-chloro-4- methylaminobenzamide (YM-09151-2) completely reverse the effects of PCP, whereas the same dose ranges of these drugs produce sedation. 5. The dopamine D2-selective antagonist, sulpiride, has no apparent effect on the PCP latency to the rat dive. 6. Thus, PCP-induced diving behavior was improved by sigma ligands and the 5-HT2 antagonist. This model of negative symptoms in an experimental animal will facilitate experiments on drug treatments for schizophrenia.
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PMID:The sigma-selective ligand NE-100 attenuates the effect of phencyclidine in a rat diving model. 771 58

The reduction in magnitude of the startle reflex in response to a loud noise produced by prior presentation of a stimulus of lower intensity is known as prepulse inhibition (PPI). PPI may be disrupted by a variety of drugs, most notably by dopaminergic agonists such as apomorphine and by phencyclidine (PCP), and related noncompetitive N-methyl-D-aspartate (NMDA) antagonists. Apomorphine-induced disruption of PPI is antagonized by both typical and atypical neuroleptics. The present study examined the effects of the atypical neuroleptic, clozapine, alone and in combination with PCP, on PPI in rats. The results of previous studies suggest that disruption of PPI by PCP and similar drugs is not sensitive to antagonism by typical neuroleptics such as haloperidol. The results of the present study show that clozapine's effect on PCP-induced disruption of PPI is also limited. The failure of clinically effective antipsychotics of diverse chemical classes to block the effects of PCP on PPI of acoustic startle suggest that the effects of PCP in this procedure may represent a model of attentional deficits observed in treatment-resistant schizophrenia.
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PMID:Clozapine's effects on phencyclidine-induced disruption of prepulse inhibition of the acoustic startle response. 788 71

Phencyclidine (PCP)-induced behavior in rats was investigated in water maze and diving behavior tasks. The swimming and diving latencies of PCP-treated groups placed in a water maze apparatus were gradually shortened, and prolonged, respectively, while rats in a control group performed well. In all rats, stereotyped behavior and hyperlocomotion were absent. We propose that this animal model induced by lower doses of PCP may be useful for further studies to research schizophrenia.
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PMID:A rat model of phencyclidine psychosis. 796 34

Phencyclidine (PCP; angel dust) is a drug of abuse known to produce a behavioral state in humans resembling schizophrenia/psychosis. PCP is a noncompetitive NMDA receptor antagonist and produces a variety of behaviors in rats including circling. The behavioral effects of other noncompetitive NMDA receptor antagonists such as (+)-MK-801 are still being elucidated. Here, adult female rats were dosed with PCP (10 mg/kg, IP), or (+)-MK-801 (0.1 mg/kg, IP) and circling preference was recorded for 2 h before sacrifice to determine monoamine levels by HPLC/EC. Animals injected with PCP or (+)-MK-801 showed a preference to turn to the left (65% and 72%, respectively). PCP and (+)-MK-801 also produced a significant increase of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in whole striatum on both sides of the brain. Further dissection of the striatum into medioventral and dorsolateral regions revealed that HVA was increased bilaterally except in globus pallidus where we found significant increases in dopamine (DA), DOPAC, and HVA only on the left side after PCP and (+)-MK-801 administration. These data suggest that PCP and (+)-MK-801 produce a greater preference to turn left than right, a finding similar to that found in human psychosis. Furthermore, it is possible that this preference to turn toward the left hemispace is due to an asymmetry in dopamine function found in the globus pallidus after administration of PCP and similar drugs.
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PMID:Phencyclidine and (+)-MK-801-induced circling preference: correlation with monoamine levels in striatum of the rat brain. 796 37

Phencyclidine (PCP)-induced psychosis is a useful animal model for studies on schizophrenia. N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]- ethylamine monohydrochloride (NE-100) had no effect on conditioned avoidance responses (CAR) in rats, whereas, the PCP-induced impairment of avoidance inhibition was attenuated by NE-100. The PCP-induced ataxia or decreased attention in rhesus monkeys was to some extent overcome by NE-100. In dogs, PCP-induced either head-weaving behavior or ataxia, effects which were blocked by NE-100. Administration of PCP led to an increase in beta-2 and a decrease in delta relative power (RP) activity in cortical background spectral electroencephalographics (ECoG) in dogs. While NE-100 in itself showed no significant change in beta-2 and delta RP, NE-100 did block the PCP-induced beta-2 increase and delta decrease. These findings indicate that NE-100 attenuates the effect of PCP in experimental animals. This drug is being considered as a therapeutic for the treatment of patients in the schizophrenia.
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PMID:NE-100, a novel sigma receptor ligand: effect on phencyclidine-induced behaviors in rats, dogs and monkeys. 804 Dec 25

N-allylnormetazocine (SKF-10047) and related benzomorphans induce psychotomimetic effects in animals and humans, and bind a unique, non-opioid receptor, denoted the sigma site. Sigma receptors have been found in the cortical and limbic structures in human postmortem brain: their anatomical distribution is different from phencyclidine (PCP) sites. Sigma receptors regulate not only dopamine, excitatory amino acid and PCP receptors, but also interact neuropeptides. Endogenous sigma ligands are not yet determined. Isolation and cloning of the receptor genes have not yet been successful. Selective loss of cerebral cortical sigma, but not PCP binding sites, has been observed in schizophrenia. A more compelling role for sigma sites in schizophrenia is indicated by the high affinity of some neuroleptic drugs, including haloperidol, for sigma sites. Rimcazole, a weak but selective sigma ligand, has very good clinical efficacy as a neuroleptic agent and has few side effects. Thus, sigma ligands may be useful in the treatment of schizophrenia. The present review describes properties of sigma receptors and its roles in relation to sigma ligands in the regulation of the central nervous system on the basis of the results of more recent studies.
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PMID:[Physiological function of sigma receptors: central pharmacological effects of sigma ligands]. 804 46

Phencyclidine (PCP) produces schizophreniform psychoses in drug abusers and exacerbates symptoms in chronic schizophrenics. Although the exact mechanisms of psychotomimetic effects are unknown, the drug is known to act as an indirect dopamine (DA) agonist by inhibiting neuronal reuptake of DA. The drug is also known to work as a N-methyl-D-aspartate (NMDA) antagonist. Aiming to investigate characteristics of these two properties of PCP in the same experimental system, the effects of PCP on spontaneous and NMDA-induced DA efflux from superfused slices of rat striatum were examined. DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in the superfusate samples were extracted via alumina extraction and measured by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). PCP, at concentrations greater than 1 microM, produced a concentration-dependent increase of the spontaneous efflux of DA. DOPAC efflux was also concentration-dependently increased by PCP. However, PCP inhibited DA efflux induced by NMDA even at a low concentration (0.1 microM), which did not alter the spontaneous efflux of the transmitter. The mode of the inhibition of PCP was shown to be noncompetitive with an estimated IC 50 value of 280 nM. These results indicate that PCP acts simultaneously as a weak indirect DA agonist and as a potent noncompetitive NMDA antagonist. Since psychological change in normal subjects or exacerbation of schizophrenic symptoms has been reported to occur with a small dose of PCP, the psychotomimetic effects of the drug are more likely to be mediated by its interaction with NMDA receptor. The clinical significance of the present study is discussed in relation with the qlutamatergic hypothesis of schizophrenia.
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PMID:[A study on the pharmacological action of phencyclidine]. 809 62


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