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)

Several pieces of evidence support the view that GABA neurons inhibit the DA system both in extrapyramidal and limbic regions. This inhibition is exerted on cell bodies and terminals of DA neurons and is involved in the regulation of their activity. A recently synthesized GABAmimetic compound SL 76.002 has considerably helped in elucidating the role of GABA in this regulation as well as the therapeutic implication of changes of GABAergic transmission in human brain. Thus, impairment of dopaminergic transmission by SL 76.002 has been shown to be effective in iatrogenic extrapyramidal syndromes such as L-DOPA-induced involuntary movements in parkinsonian patients and neuroleptic-induced tardive dyskinesias: the first attributed to an exaggerated formation and liberation of DA, the second to supersensitivity of target cells of DA neurons. Furthermore, GABAergic medication has been confirmed to be useful in Huntington's chorea in which some symptoms originate from degeneration of striatal GABAergic neurons. Finally, GABAergic inhibition on cellular excitability has been proved to ameliorate epilepsy. However, SL 76.002, contrary to the expectation, was not effective in schizophrenia suggesting that GABA does not play a major role in the pathogenesis of this disorder.
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PMID:[Potential therapeutic activity of GABA-mimetic drugs in neuropsychiatry]. 4 43

1. The treatment of schizophrenic symptoms has not the same efficacy in acute and chronic phases of the disease and on the various target symptoms of schizophrenia. 2. The ideal antipsychotic drug might have different properties, sometimes contradictory, to be effective both on paranoid and hebephrenic symptoms which seem to be a mirror image of the same disorder. 3. Basic perspectives in the chemotherapy of schizophrenic psychoses must be founded on better methodological considerations in clinical trials, on a better use of antipsychotic drugs with the help of pharmacokinetic data and computerized EEG and also on new neurochemical findings. 4. Recent data on the mode of action of neuroleptics open up new therapeutic classes of drugs. Such are GABA-like drugs and, more recently, beta-blockers.
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PMID:Perspectives in chemotherapy of schizophrenic psychoses. 4 63

21 schizophrenic patients were treated in a single blind study with para-chlorphenyl-GABA (baclofen) for 20 days after a placebo period of at least 1 week. Global clinical impression identified five patients as behaviorally unchanged, seven as improved and nine as worsened during the active drug administration. Four patients had to be withdrawn from the trial because of serious and unmanageable psychotic exacerbations. Overall incidence of psychotic symptoms in the group of the schizophrenic patients did not change substantially neither did the remission coefficient as calculated from the AMP documentation system. No differential effect was detected either on selected Schneiderian first rank symptoms or on symptoms more characteristic for chronic defectuous schizophrenia. It is concluded that baclofen is not a useful drug in the therapy of schizophrenia.
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PMID:Baclofen (para-chlorphenyl-GABA) in schizophrenia. 32 92

gamma-Aminobutyric acid (Gaba) has been shown to influence dopamine activity in the brain. The author suggests that Gaba could be involved in the hypothesized dopamine hyperactivity in schizophrenia. He discusses pharmacological interventions that may raise Gaba-mediated function in the brain and states that further development of Gaba analogues seems clearly indicated. It is conceivable, he concludes, that these compounds could enhance the antipsychotic activity of dopamine receptor blockers, which could lead to the use of lower doses and therefore fewer extrapyramidal side effects.
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PMID:gamma-Aminobutyric acid (Gaba) and the dopamine hypothesis of schizophrenia. 83 33

Changes in dopamine (DA) turnover have been studied in rats after treatment with pimozide and/or gabergic drugs such as beta-(p-chlorophenyl)-GABA and aminooxyacetic acid using the tyrosine-hydroxylase inhibitor alpha-methyltyrosine and methylester (H44/68). The changes in DA levels were determined by quantitative microfluorimetrical analysis of the fluorescence in various DA terminal systems. Beta-(p-chlorophenyl)-GABA (5--20 mg/kg) and aminooxyacetic acid (25 mg/kg) counteracted the pimozide (1 mg/kg) induced increase in DA turnover in subcortical and cortical limbic regions but not in the caput of the caudatus. These findings indicate the existence of a strong and preferential inhibitory gabergic control of the mesolimbic DA neurons and offer the possibility of improving the treatment of schizophrenia provided that limbic DA receptors are involved in this disease. If so, lesions of gabergic pathways may exist in the schizophrenic brain.
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PMID:Evidence for an inhibitory gabergic control of the meso-limbic dopamine neurons: possibility of improving treatment of schizophrenia by combined treatment with neuroleptics and gabergic drugs. 116 Apr 12

Previous studies from our laboratory indicated that the veratridine-induced release of glutamate and GABA from synaptosomes derived from brains of schizophrenics was decreased. In the present study, synaptosomes were prepared from frozen brain samples from schizophrenics and from controls. Stimulation by 10 mumol/L 2-amino-3-hydroxy-5-methoxylisoxazole-4-propionic acid (AMPA) produced equal glutamate release from both groups. Release induced by either 10 mumol/L kainic acid (KA) or n-methyl-d-asparate (NMDA) was reduced significantly in the preparations derived from schizophrenics. Similarly, the amount of GABA released by 50 mumol/L glutamate was also reduced in the schizophrenic-derived synaptosomes. However, in membranes derived from the crude synaptosomal pellet, no differences between the controls and schizophrenics were observed in measures of total glutamate binding or its displacement by NMDA. The data demonstrate a deficiency in NMDA (and possibly KA) receptor functioning schizophrenics and support the "second-generation" theories of schizophrenia as a glutamatergic deficiency disorder.
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PMID:Deficient NMDA-mediated glutamate release from synaptosomes of schizophrenics. 168 12

Virtually all antidepressant and antipsychotic drugs, including clozapine, rimcazole and lithium ion, are proconvulsants, and convulsive therapy, using metrazol, a known GABA-A antagonist, as well as electro-convulsive therapy, can be effective in treating both schizophrenia and affective psychoses. Many antidepressant and antipsychotic drugs, including clozapine, as well as some of their metabolites, reverse the inhibitory effect of GABA on 35S-TBPS binding, a reliable predictor of GABA-A receptor blockade. A review of relevant literature suggests that 1) "functional" psychoses constitute a continuum of disorders ranging from schizophrenia to affective psychoses with overlap of symptoms, heredity and treatments, 2) a weakening of GABergic inhibitory activity, or potentiation of counterbalancing glutamatergic neurotransmission, in the brain, may be involved in the therapeutic activities of both antidepressant and antipsychotic drugs, and 3) schizophrenia and the affective psychoses may be different expressions of the same underlying defect: GABergic preponderance/glutamatergic deficit. Schizophrenia and affective psychoses share the following: 1) several treatments are effective in both, 2) similar modes of inheritance, 3) congruent seasonal birth excesses, 4) enlarged cerebral ventricles and cerebellar vermian atrophy, 5) dexamethasone non-suppression. Both genetic and environmental factors are involved in both schizophrenia and affective psychoses, and several lines of evidence suggest that important environmental factors are neurotropic pathogens that selectively destroy glutamatergic neurons. One group of genes associated with psychoses may increase vulnerability to attack and destruction, by neurotropic pathogens, of excitatory glutamatergic neurons that counterbalance inhibitory GABergic neurons. A second group of genes may encode subunits of overactive GABA-A receptors, while a third group of genes may encode subunits of hypo-active glutamate receptors. Improved antipsychotic drugs may be found among selective blockers of GABA-A receptor subtypes and/or enhancers of glutamatergic neurotransmission. A mechanism similar to kindling, leading to long-lasting reduction of GABergic inhibition in the brain, may be involved in several treatments of psychoses.
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PMID:A review of evidence for GABergic predominance/glutamatergic deficit as a common etiological factor in both schizophrenia and affective psychoses: more support for a continuum hypothesis of "functional" psychosis. 168 35

Benzodiazepines are generally well tolerated (compared to barbiturates or antidepressants, their side-effects are milder). They may be used safely, their toxicity is low. Benzodiazepine overdosage may be lethal only if the drug is taken simultaneously with other drugs or alcohol. They act primarily through inhibiting the GABA system, their anxiolytic and sedative effects are of primary importance from the psychiatric aspect. Their classification is based on the difference in their receptor affinity (potency) and kinetics. Derivatives of low, medium and high potency are known. The introduction of high potency benzodiazepines in psychiatry has increased the therapeutic means. The major field of indication of benzodiazepine therapy is DSM-III anxiety disorders and insomnias but they may be successfully used in the treatment of manic conditions, schizophrenia, delirium tremens, clinical conditions accompanied by anxiety-depression, acute restlessness, neuroleptic-induced acute distonias, and akathisias. Even if therapeutic doses are used, tolerance to benzodiazepines may develop after some weeks of therapy. The general withdrawal symptoms are not severe, but the rebound symptoms often hinder the discontinuance of the drug or the reduction of doses. When prescribing benzodiazepines the risk of long-term therapy and the prevention of the development of drug addiction have to be considered.
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PMID:Use of benzodiazepines in psychiatry. 181 22

The syndrome of "painful legs and moving toes" is characterised by spontaneous causalgic pain in the lower extremities associated with peculiar involuntary movements of the toes and feet. It has been observed after a variety of lesions affecting the posterior nerve roots, the spinal ganglia and the peripheral nerves. The pathophysiology of the syndrome is unknown. I report a patient who developed the syndrome during treatment for schizophrenia with the antipsychotic agent molindone hydrochloride. The patient's response to the combination of clonazepam and baclofen suggests that the pathophysiology of the "painful legs and moving toes" may be linked to impairment of spinal serotonergic and GABA functions.
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PMID:Neuroleptic-induced "painful legs and moving toes" syndrome: successful treatment with clonazepam and baclofen. 208 81

Four cases of resistant Schizophrenia treated with valproate association with different neuroleptic drugs (thioridazine in three cases and loxapine in one) are presented. After a mean period of three months with this treatment, clinical improvement, consisting in a reduction of positive symptoms, as measured by the BPRS, and a normalization of hostile/disruptive behavior, was observed, and hospital discharge was possible. Reduction of symptoms was still present after a follow-up of 4 to 24 months. As valproate is a drug with gabaergic properties, a GABA involvement in the pathogenesis of schizophrenia is discussed. The association of valproate to neuroleptic drugs should be considered in the treatment of resistant Schizophrenia.
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PMID:Treatment of resistant schizophrenia with valproate and neuroleptic drugs. 257 9


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