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)

Amantadine was introduced for the pharmacological management of neuroleptic malignant syndrome (NMS) because of its beneficial effects in Parkinson's disease which were attributed to dopaminomimetic properties. While the dopaminomimetic effects of amantadine are weak under experimental conditions, recent studies have confirmed that amantadine is an antagonist at the N-methyl-D-aspartate (NMDA) type of the glutamate receptor. Amantadine has psychotomimetic properties in patients with Parkinson's disease and normal controls. Two of four patients who received amantadine for NMS suffered an exacerbation of their psychiatric illness. Our observations support the glutamate hypothesis of schizophrenia which suggests that reduced glutamatergic transmission causes a relative dopaminergic excess in the basal ganglia and the limbic system.
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PMID:Amantadine and the glutamate hypothesis of schizophrenia. Experiences in the treatment of neuroleptic malignant syndrome. 810 Oct 93

The antipsychotic drugs (APDs) are fundamental tools in current psychiatric practice. A new generation of agents, the atypical APDs, represents an important progress in the treatment of psychotic disorders. Unfortunately, some of them induce excessive body weight gain (BWG), obesity, hyperglycemia and dyslipidemia in the following order: clozapine approximately equal to olanzapine > quetiapine > risperidone > ziprasidone = aripiprazole. Appetite stimulation is probably the main mechanism of BWG and this is strongly correlated with the APD affinity for H1 (histaminergic) and alpha1 (adrenergic) receptors. A composed ratio of the APD affinity for diverse neurotransmitters involved in food intake (FI) regulation correlates with BWG as well. Endocrine/metabolic mechanisms, such as the activation of the hypothalamus-pituitary-adrenal axis, changes in insulin sensitivity (by conventional and atypical agents), hyperprolactinemia and gonadal dysfunction (by conventional APDs and risperidone) may also be involved. Importantly, patients with schizophrenia may have a genetically-based predisposition to appetite dysregulation, insulin resistance and endocrine imbalance involving gonadal steroids. Excessive BWG must be prevented or attenuated by proper drug selection, combining or switching agents, nutritional assistance and physical exercise. Amantadine. metformin and reboxetine proved to significantly lessen APD-induced BWG. Notwithstanding this, novel strategies are necessary to treat this side effect in a clinical population particularly prone to poor compliance and under a high risk of negative drug interaction.
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PMID:Drug induced weight gain, an impediment to successful pharmacotherapy: focus on antipsychotics. 1505 13

The present study aimed to test the hypothesis that dopamine agonists may enhance cognitive function. The effect of amantadine on neuropsychological function in medicated schizophrenia patients was investigated. The study comprised an add-on, double-blind, placebo-controlled, cross-over 6-week trial. Participants comprised 29 inpatients at Sha'ar Menashe Mental Health Center who were diagnosed with chronic schizophrenia or schizoaffective disorder. Amantadine 200 mg/day or identical placebo was added to ongoing antipsychotic treatment for 3 weeks. Study medications were then switched for an additional 3 weeks. Assessments were performed at baseline, and weeks 3 and 6, including cognitive and visuomotor assessments. Clinical ratings included positive, negative and depressive symptoms and extrapyramidal side-effects. Blood prolactin levels were assayed. A mixed model was used to examine differences in the data at the three assessment points. Amantadine was associated with improved visuomotor coordination compared to placebo. No significant changes in cognitive functions were noted. Clinical symptoms, extrapyramidal side-effects and blood prolactin levels were not altered. Amantadine improved visuomotor coordination independently of extrapyramidal side-effects but not cognitive function. Because prolactin concentrations were unchanged, the mechanism is more likely to involve glutaminergic NMDA than dopaminergic mechanisms. Further studies of amantadine with different doses and treatment duration, as well as more glutamate selective agents such as memantine, are indicated.
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PMID:A double-blind, cross-over comparison of the effects of amantadine or placebo on visuomotor and cognitive function in medicated schizophrenia patients. 1619 41