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)

An autopsy case of malnutrition with spinal tract degeneration confined to the bilateral posterior columns is reported. The patient had schizophrenia in adolescence, and suffered from aplastic anemia in late middle age. Subsequently, he took little food due to delusions for 18 months until his death. He had malnutrition resulting in severe hypoproteinemia. He developed gait disturbance, loss of deep tendon reflexes and paresthesia of limbs. Neuropathological examination disclosed tract degeneration confined to the bilateral spinal posterior columns, in addition to the findings of aplastic anemia and hypoxic encephalopathy in the cerebrum. The myelin and axons were severely affected throughout the spinal cord; status spongiosus with many fatty-laden macrophages was seen in these lesions. Neurons in the posterior column nuclei were intact, while the dorsal roots and their ganglia were moderately affected. The unusual distribution and extension of the degeneration of the bilateral posterior columns in the poor nutritional state is discussed.
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PMID:Spinal tract degeneration confined to the bilateral posterior columns in malnutrition: report of an autopsy. 860 40

Although antipsychotic drugs are effective in treating the so-called positive features of schizophrenia, between one-quarter and one-third of patients respond poorly. Furthermore, the incidence of adverse effects is high, especially those reflecting disruption of extrapyramidal function, and is a major source of non-compliance. There is a clear need for new compounds that are more efficacious and/or better tolerated. Until recently, the classical dopamine hypothesis, with its emphasis on D2 blockade as the key mechanism of antipsychotic action, dominated drug development, though the emphasis is now shifting. Three 'new' antipsychotics have reached the international market in the past 5 years-the newly rehabilitated clozapine and the genuinely new remoxipride and risperidone. Claims of enhanced tolerability have been made for each of these, but as none is free from adverse effects, their place in treatment can only be meaningfully established in relation to the efficacy of each in different clinical situations. Clozapine has an extensive profile of general, nonhaematological adverse effects which is slightly different in emphasis from, but comparable in incidence to, that of chlorpromazine. There is a 0.8% risk of agranulocytosis in the first year of exposure, which can be fatal, though the boundary separating it from other (especially phenothiazine) antipsychotics in this regard is becoming increasingly blurred. It has a clearly diminished liability to cause extrapyramidal adverse effects. Its proven efficacy in operationally defined treatment-resistant schizophrenia and in patients intolerant to the extrapyramidal adverse effects of standard drugs establishes its credentials for advantage in these groups. There is on present evidence, however, only a hint of enhanced efficacy in acute schizophrenia: this requires further investigation. Open maintenance studies provide impressive data on long term outcome, especially in terms of quality-of-life parameters, but this issue requires to be addressed in blind, randomised trials. Until such additional information is forthcoming the risks and consequent costs would not justify extension of its use. The evidence to date is that reported benefits in so-called negative features probably reflect its favourable neurological profile. While the advantages of clozapine are undoubted, they remain as yet restricted to selected patient groups. Remoxipride has a good general tolerability profile, its special strength being its low sedative effect. However, its reported association with aplastic anaemia has severely restricted its use, and regular haematological monitoring is required. Although remoxipride appears to have a lower liability to produce extrapyramidal adverse effects than the high potency haloperidol, its benefits relative to other low potency compounds in this regard remain unproven. The only obvious situation in which its risks and consequent costs would be justified would seem to be patients with established compliance problems as a result of intrusive sedation with standard drugs. The position of other benzamides such as raclopride and amisulpride remains to be established. Risperidone, perhaps from its antiadrenergic actions, has more in the way of cardiovascular adverse effects than haloperidol, though these can be obviated by graded early exposure. It may also be associated with greater weight gain. Otherwise it appears to be well tolerated. In comparison with haloperidol, it appears to be associated with a lower prevalence of acute extrapyramidal adverse effects in dosages < or = 10 mg/day, the most potentially important component of which is its reportedly insignificant likelihood of promoting akathisia. These conclusions emerge from comparisons with haloperidol in doses many might consider somewhat high. The question of the advantage of risperidone over low or milligram-equivalent haloperidol regimens remains open.(ABSTRACT TRUNCATED)
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PMID:Adverse effects of antipsychotic agents. Do newer agents offer advantages? 873 14

This is a review on the recent results of research on sigma-receptor antagonists. NE-100, a selective sigma1-receptor antagonist, shows improvement of abnormal behaviors and cognitive dysfunction induced by phencyclidine (PCP). However, NE-100 does not inhibit dopamine agonist-induced behaviors nor induces catalepsy. The mode of action of NE-100 is estimated to be the indirect modulation of the NMDA/PCP-receptor ion channel complex and the modulation of dopamine release from the dopaminergic nerve terminals. The recently reported MS-355/MS-377, which is also a selective sigma1-receptor antagonist, has a similar pharmacological profiles as NE-100, but in addition, MS-355/MS-377 inhibits methamphetamine-induced formation of reversal tolerance and also inhibits apomorphine-induced climbing behavior like dopamine D2-receptor antagonists. The report on clinical trial targeting schizophrenia shows results on rimcazole, remoxipride, BMY 14802, panamesine (EMD 57445) and SL 82.0715. Rimcazole was effective in the open study, but the double blind trial was discontinued due to seizure induction. Remoxipride showed efficacy different from those of dopamine D2-receptor antagonists (less extrapyramidal adverse effects), but the trial was discontinued due to occurrence of aplastic anemia. Panamesine and SL 82.0714 showed favorable efficacy in the open studies, but BMY 14802 showed no efficacy in clinical trials.
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PMID:[Atypical antipsychotic profiles of sigma receptor ligands]. 1056 61

Remoxipride is a substituted benzamide that acts as a weak but very selective antagonist of dopamine D2 receptors. It was introduced by Astra (Roxiam) at the end of the eighties and was prescribed as an atypical antipsychotic. This article reviews its putative selective effects on mesolimbic versus nigrostriatal dopaminergic systems. In animals, remoxipride has minimal cataleptic effects at doses that block dopamine agonist-induced hyperactivity. These findings are predictive of antipsychotic activity with a low likelihood of extrapyramidal symptoms. Remoxipride also appears to be effective in more recent animal models of schizophrenia, such as latent inhibition or prepulse inhibition. In clinical studies, remoxipride shows a relatively low incidence of extrapyramidal side effects and its effects on prolactin release are short-lasting and generally mild. The clinical efficacy of remoxipride is similar to that of haloperidol or chlorpromazine. Although its clinical use was severely restricted in 1993, due to reports of aplastic anemia in some patients receiving remoxipride, this drug has been found to exhibit relatively high selectivity for dopamine D2 receptors making remoxipride an interesting tool for neurochemical and behavioral studies.
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PMID:Pharmacology of the atypical antipsychotic remoxipride, a dopamine D2 receptor antagonist. 1160 43