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)

MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo-(a,d)cyclohepten-5,10-imi ne hydrogen maleate], which blocks glutamatergic transmission at the NMDA-receptor-gated ion channel, induced stereotypies which are similar to those found after intrastriatal injections of AP-5, e.g. sniffing and locomotion. Tests in familiar or unfamiliar environment (non-stressful or stressful situation) did not qualitatively change MK-801-induced effects. Haloperidol (0.1 mg/kg, IP) delayed the onset and shortened the duration of MK-801 (0.16; 0.33 mg/kg, IP)-induced stereotypy whereas clozapine (5 mg/kg, SC) potently antagonized it. However, exact quantification of sniffing, measured in an experimental chamber designed for this purpose, revealed an antagonism by both drugs, haloperidol as well as clozapine. Stereotypy is considered to represent an animal model of schizophrenia, and the antagonism of stereotypy with classical (haloperidol) as well as with atypical (clozapine) antipsychotic drugs is in accordance with the glutamate hypothesis of schizophrenia.
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PMID:MK-801-induced stereotypy and its antagonism by neuroleptic drugs. 197 47

Nuclear magnetic resonance produced by a FONAR QED 80 whole-body scanner with measurement in vivo of T1 proton relaxation time was used in 20 patients with the clinical diagnosis of bipolar affective disorder. Diagnoses were based on Research Diagnostic Criteria, Diagnostic Statistical Manual III code 296.66, and on Schedule for Affective Disorders and Schizophrenia. Proton T1 relaxation times were measured in all patients and in 18 normal controls before and after lithium carbonate treatment. Normal values of T1 in frontal and temporal lobes were 210 +/- 10 msec. All but three patients had prelithium T1 values higher than the controls (264 +/- 8.8 msec). After lithium therapy of 900 mg/day for 10 days, serum lithium levels were in the therapeutic range of 0.5-1.5 mEq/L, and patient T1 values were near normal levels (208 +/- 8.0 msec). One patient with a prelithium level within normal range proved to have cyclothymic disorder and not bipolar affective disorder; two patients did not complete the study. This study shows a statistically significant difference (p less than 0.01) in the behavior of hydrogen protons in bipolar affective disorder, which has not previously been reported in medical literature.
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PMID:Nuclear magnetic resonance in bipolar affective disorders. 641 Jul 8

1. The efficacy of butoctamide hydrogen succinate (BAHS) was compared with that of nitrazepam on the basis of the polysomnograms and the subjective assessments. 2. Twelve healthy male students were divided into three groups consisting of 4 subjects each with were administered BAHS 600 mg, nitrazepam 5 mg, and BAHS 600 mg + nitrazepam 5 mg, respectively. 3. Polygraphic recordings were made for 8 consecutive nights for each subject, and the polysomnograms were evaluated by computerized automatic analysis using the interval histogram method. 4. An inert placebo was administered on the first 3 nights and on the seventh and eighth nights, and the test article regimen was administered on the fourth, fifth and sixth nights. 5. The test articles and the placebo were administered orally at 22:30 hr, and the recording of polysomnograms was started at 23:00 hr and ended at 8:00 hr the next morning. 6. The subjects were requested to fill out the subjective assessment of sleep before falling asleep and after arising the next morning. 7. BAHS increased REM sleep and decreased stage 2 sleep significantly; however, it failed to affect stage 1, 3 or 4 sleep. 8. Nitrazepam increased significantly the total sleep time and stage 2 sleep but decreased significantly the stage 3 sleep and decreased slightly the stages 1, 4 and REM sleep. 9. The combined treatment with BAHS and nitrazepam did not alter the sleep parameters except for increasing the total sleep time. 10. No obvious changes were observed in the subjective assessments after administration of the drugs. 11. These findings suggest that BAHS results in a unique sleep pattern different from benzodiazepines, and that BAHS may be suitable for treating insomnia in elderly patients and those with drug abuse, manic-depressive illness or schizophrenia.
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PMID:Stimulatory effect of butoctamide hydrogen succinate on REM sleep in normal humans. 762 90

The dopamine and glutamate hypotheses are two pharmacological models for schizophrenia. In the present investigations, the prepulse inhibition paradigm was used to evaluate the role of the nucleus accumbens core region in both models. Prepulse inhibition is known to be decreased in schizophrenics, when compared with control patients, and in rats after systemic injection of dopamine receptor agonists and non-competitive antagonists of the NMDA receptor. In the present study injection of dopamine in the rat nucleus accumbens core region also decreased prepulse inhibition. Injections of NMDA decreased, whereas a low dose of the competitive NMDA receptor antagonist (+/-)-2-amino-5-phosphonopentanoic acid (AP-5) and the non-competitive NMDA receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydroxy-5H-dibenzo[a,d]cyclohepten-5 ,10-imine hydrogen maleate (MK-801) increased prepulse inhibition. The results indicate an involvement of the accumbens core in mediating the systemic effects on prepulse inhibition of dopamine receptor agonists but not of non-competitive NMDA receptor antagonists.
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PMID:Changes in prepulse inhibition after local administration of NMDA receptor ligands in the core region of the rat nucleus accumbens. 771 56

Previous studies in schizophrenic patients have suggested that there are changes in olfactory sensitivity. In order to externally validate a psychometrical assessment of the psychosis-risk indicated by schizotypic factors, this study was carried out to determine whether changes in olfactory perception could be determined even for persons merely at risk of developing schizophrenia. These 'psychosis-prone' subjects consistently scored high in either the scale for 'physical anhedonia' (PA) or the scale for 'perceptual aberration' (PAB). Thus, three groups were investigated (control, n = 11; PA, n = 12; PAB, n = 12). Each subject participated in one testing session where the two odorants, vanillin (pleasant) and hydrogen sulphide (unpleasant), were applied by means of a specially designed delivery apparatus. Subjects rated both the intensity and the hedonic quality of the stimuli. In addition, olfactory event-related potentials (OERP) were recorded after dichotomous stimulation. In general, there were only few significant differences between the three groups investigated. Contrary to expectations, ratings for pleasantness of vanillin were highest in PA subjects compared to PAB subjects and controls (p < 0.05). Correspondingly, OERP amplitudes in response to vanillin were largest within the PA group (p < 0.05). For hydrogen sulphide, PAB subjects showed the smallest OERP amplitudes (p < 0.05). In addition, it was observed that female subjects had significantly larger OERP amplitudes when compared to male subjects (p < 0.05), which possibly indicates gender differences in olfactory sensitivity.
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PMID:Olfactory event-related potentials in psychosis-prone subjects. 840 34

The influence of three selective monoamine receptor antagonists on spontaneous locomotion and on the hyperlocomotion induced by the un-competitive N-methyl-D-aspartate (NMDA) receptor antagonist [+]-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]-cyclohepten-5,10-imine hydrogen maleate (MK-801; dizocilpine) was investigated. The selective and potent 5-hydroxytryptamine (5-HT)2A receptor antagonist R(+)-alpha(2,3-dimethoxyphenyl)-1-[2(4-fluorophenyl)ethyl)]-4-piperidine -methanol (MDL100,907; M100907) displayed a clear-cut selectivity for reduction of MK-801-induced as compared to spontaneous locomotion, in that the former was dose-dependently (0.001, 0.01, 0.1 mg/kg i.p.) blocked and even totally abolished by the highest dose, while the latter was only modestly affected. Even at high doses of M100907 (up to 9 mg/kg i.p.), spontaneous locomotion was not reduced below 40% of control. The selective dopamine D1 receptor antagonist (-)-[4aR, 10 aR]-1,2,3,4,4a,5,10,10a-octahydro-4-(4-chloro-2-methyl-phenyl)-1-methyl- benzo[g]quinoxaline-6-ol (SDZ PSD 958; 0.017, 0.15, 1.35 mg/kg i.p.) decreased both spontaneous and MK-801-induced locomotion with a slight preference for the latter; spontaneous locomotion was dose-dependently diminished to approx. 10% of controls (at 8 mg/kg i.p.). The dopamine D2 receptor antagonist raclopride ([(-)-(S)-3,5-dichloro-N-((1-ethyl-2-pyrrolidinyl) methyl)-6-methoxy-salicylamide tartrate]; 0.11, 0.33, 1.0 mg/kg i.p.) reduced both MK-801-induced and spontaneous locomotion to a similar extent. An orthogonal matrix experimental design, and multiple regression, were used to evaluate the effects of several combinations of different doses of the 5-HT2A receptor antagonist and the dopamine D1 receptor antagonist. No synergistic actions on reduction of spontaneous or MK-801-induced locomotion were detected between M100907 and SDZ PSD 958. If the hyperlocomotion elicited by acutely administered MK-801 is a valid model of at least some aspects of schizophrenia, these results indicate that the 5-HT2A receptor antagonist M100907 will have efficacy in treating this condition. The lack of effect on spontaneous locomotion, suggests that M100907, compared to dopamine receptor antagonists, will be less prone to induce psychomotor side-effects. Ongoing clinical studies will hopefully give the answers in the near future.
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PMID:MK-801-induced hyperlocomotion: differential effects of M100907, SDZ PSD 958 and raclopride. 936 62

To examine whether antioxidant capacity is reduced in patients with schizophrenia, we determined plasma total antioxidant status (TAS) by quenching the absorbance of the radical cation formed by the reaction of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) with a metmyoglobin and hydrogen peroxide. TAS serves as an index of net antioxidant activity derived from various antioxidants in plasma. Male schizophrenic patients were compared with age- and sex-matched healthy control subjects, using a within-subject, repeated measures, on-off-on haloperidol treatment design. Drug-free patients were free of all psychotropic medications for an average of 32 days. Plasma TAS was significantly lower in patients with schizophrenia than in normal controls. Plasma TAS in patients was significantly and inversely correlated with symptom severity during the drug-free condition. There were no significant differences between on and off haloperidol-treatment conditions. When patients returned to haloperidol treatment after relapse, the plasma TAS remained fairly constant and was not significantly different from the same individuals during haloperidol-stabilization or drug-free periods. These findings are indicative of an impaired antioxidant defense system, not attributable to neuroleptic treatment, and lend further support to the notion that oxidative stress may have a pathophysiological role in schizophrenia.
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PMID:Reduced status of plasma total antioxidant capacity in schizophrenia. 1070 48

This paper reviews what is currently known about the redox state of the glutamate synapse and its possible role in modulating synaptic plasticity and thus learning and neurocomputation. The hypothesis is presented that the growth or pruning of the synaptic spine is controlled in part by the balance in the synapse between neurodestructive pro-oxidants (e.g., nitric acid radical and hydrogen peroxide) and neuroprotective antioxidants (e.g., ascorbate and carnosine). In addition, there may be a role for catecholamines, in particular dopamine, related to its role in reinforcement signalling. Activation of the dopamine D2 receptor induces the synthesis of an antioxidant enzyme, possibly catalase. Dopamine may also affect the redox balance in the glutamate synapse directly by diffusion from the adjacent dopaminergic bouton-en-passage. Catecholamines are powerful antioxidants, scavengers of free radicals and iron chelators. Catecholamine-iron complexes are potent dismuters of superoxide ions. Additional agents participating in spine pruning may be neurotoxic catecholamine o-quinones present in the brain. This system may be at fault in schizophrenia and Parkinson's disease. Experiments to test the hypothesis are suggested.
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PMID:Redox mechanisms at the glutamate synapse and their significance: a review. 1032 73

Proton magnetic resonance spectroscopy (MRS) has become an important tool to study in vivo certain biochemical aspects of brain disorders. In the last decade this technique has been applied to the in vivo investigation of pathophysiological aspects of psychiatric disorders, extending knowledge of the related brain alterations. This review will focus on providing some background to clarify technical and biochemical issues and it will describe the studies that have been performed in schizophrenia. The results will be framed in a more general context to highlight what we have learned and what remains to be understood from the application of this technique to schizophrenia.
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PMID:Proton magnetic resonance spectroscopy in schizophrenia. 1040 94

Quantitative magnetic resonance imaging (MRI) can measure total gray matter volume but cannot discriminate between neurons and glia. Proton magnetic resonance spectroscopic imaging (1H MRSI) measures N-acetylaspartate (NAA) which is a selective marker of neuronal loss or neuronal dysfunction. The objective of this study was to obtain quantitative measures of hippocampal volume and hippocampal NAA to determine if there was evidence for hippocampal neuronal dysfunction or neuronal loss in schizophrenia. Quantitative MRI and 1H MRSI was performed on the right and left hippocampal regions in 23 chronic schizophrenic patients and 18 control subjects. Relative to the control group, the patients with schizophrenia demonstrated no change in hippocampal volumes bilaterally, but significantly decreased NAA in the hippocampal regions bilaterally. There was also no correlation between hippocampal volumes and NAA in either the schizophrenics or controls. These findings suggest that: (1) hippocampal NAA may be a more sensitive measure of neuronal loss than volumetric measurements; and (2) reduced hippocampal NAA may be measuring neuronal dysfunction or damage rather than neuronal loss in this sample of schizophrenics.
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PMID:Reduced hippocampal N-acetylaspartate without volume loss in schizophrenia. 1040 93


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