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)

The negative symptoms of schizophrenia remain a major clinical challenge. Reboxetine is an antidepressant whose major mechanism of action is as a noradrenergic reuptake inhibitor. This study was a 6-week randomized placebo-controlled trial of reboxetine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia. The trial failed to demonstrate any significant difference between the placebo and reboxetine groups on any of the outcome measures. This trial does not suggest that increased noradreneregic drive mediated by reuptake inhibition in patients taking dopamine antagonists is of therapeutic value in schizophrenia.
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PMID:Reboxetine add on therapy to haloperidol in the treatment of schizophrenia: a preliminary double-blind randomized placebo-controlled study. 1155 70

The effect of reboxetine on steady-state plasma concentrations of the atypical antipsychotics clozapine and risperidone was studied in 14 patients with schizophrenia or schizoaffective disorder with associated depressive symptoms. Seven patients stabilized on clozapine therapy (250-500 mg/day) and seven receiving risperidone (4-6 mg/day) were given additional reboxetine (8 mg/day). After 4 weeks of reboxetine therapy, mean plasma concentrations of clozapine, norclozapine, and risperidone active moiety (sum of concentrations of risperidone and 9-hydroxyrisperidone) increased slightly but not significantly by 5%, 2%, and 10%, respectively. The mean plasma clozapine/norclozapine and risperidone/9-hydroxyrisperidone ratios were not modified during reboxetine treatment. Reboxetine coadministration with either clozapine or risperidone was well tolerated. These findings indicate that reboxetine has minimal effects on the metabolism of clozapine and risperidone and may be added safely to patients receiving maintenance treatment with these two antipsychotics.
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PMID:No effect of reboxetine on plasma concentrations of clozapine, risperidone, and their active metabolites. 1180 3

We have previously observed that addition of an alpha(2)-adrenoceptor antagonist to a selective dopamine (DA) D(2) receptor antagonist enhances the antipsychotic-like effect of the D(2) blocker and also selectively increases DA output in the medial prefrontal cortex (mPFC) in rats. These data also correlate well with previous clinical trials showing augmentation by an equivalent drug combination in schizophrenia. Since the selective noradrenaline reuptake inhibitor reboxetine was found to cause similar effects on the mesolimbocortical DA system as alpha(2)-adrenoceptor antagonists, the present study was undertaken to explore whether also reboxetine might augment the effect of the DA D(2) receptor antagonist raclopride in the same preclinical model of antipsychotic activity, the conditioned avoidance response (CAR) test. We also investigated the effect of this combination in the catalepsy test for extrapyramidal side effect liability, as well as on DA output in the mPFC and the nucleus accumbens, respectively. Reboxetine (6 mg/kg, i.p.) significantly enhanced the suppressant effect of raclopride (0.1 mg/kg, s.c.) on CAR without affecting catalepsy. Administration of raclopride (0.1 mg/kg, s.c.) to rats pretreated with reboxetine (6 mg/kg, i.p.) resulted in a greatly enhanced effect on DA output in the mPFC but not in the nucleus accumbens when compared with raclopride alone. Consequently, these results suggest that noradrenaline reuptake inhibition may provide means of augmenting the efficacy of classical D(2)-antagonists in the treatment of schizophrenia, and, in principle, to generate an atypical antipsychotic drug profile.
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PMID:Noradrenaline reuptake inhibition enhances the antipsychotic-like effect of raclopride and potentiates D2-blockage-induced dopamine release in the medial prefrontal cortex of the rat. 1243 44

The noradrenergic (NE) system mediates cognitive dysfunction in schizophrenia patients, and the NE transporter represents a putative target for cognitive enhancing therapy. In a double-blind placebo-controlled study we evaluated the effect of add-on reboxetine (4 mg/day), a selective norepinephrine reuptake inhibitor (NRI), co-administered with atypical antipsychotic olanzapine (10 mg/day) on cognitive functioning in DSM-IV schizophrenia patients. The Automated Neuropsychological Assessment Metrics battery and Wisconsin Card Sorting Test were used to assess selective cognitive functions at baseline and endpoint (6 weeks). Clinical assessment was also performed. No between-group differences were found in neurocognitive tests, suggesting that reboxetine did not significantly change patients' cognitive performance compared to placebo. Reboxetine was well-tolerated and did not interfere with the therapeutic effect of olanzapine. Long-term studies using higher reboxetine dosages and alternative NRIs (e.g., atomoxetine) are needed to determine the role of NRIs as cognitive enhancers in patients with schizophrenia and other disorders associated with cognitive impairments.
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PMID:Effect of the selective norepinephrine reuptake inhibitor reboxetine on cognitive dysfunction in schizophrenia patients: an add-on, double-blind placebo-controlled study. 2003 23

Preclinical data have shown that addition of the selective norepinephrine transporter (NET) inhibitor reboxetine increases the antipsychotic-like effect of the D(2/3) antagonist raclopride and, in parallel, enhances cortical dopamine output. Subsequent clinical results suggested that adding reboxetine to stable treatments with various antipsychotic drugs (APDs) may improve positive, negative and depressive symptoms in schizophrenia. In this study, we investigated in rats the effects of adding reboxetine to the second-generation APD olanzapine on: (i) antipsychotic efficacy, using the conditioned avoidance response (CAR) test, (ii) extrapyramidal side effect (EPS) liability, using a catalepsy test, (iii) dopamine efflux in the medial prefrontal cortex and the nucleus accumbens, using in vivo microdialysis in freely moving animals and (iv) cortical N-methyl-D-aspartate (NMDA) receptor-mediated transmission, using intracellular electrophysiological recording in vitro. Reboxetine (6 mg/kg) enhanced the suppression of CAR induced by a suboptimal dose (1.25 mg/kg), but not an optimal (2.5 mg/kg) dose of olanzapine without any concomitant catalepsy. Addition of reboxetine to the low dose of olanzapine also markedly increased cortical dopamine outflow and facilitated prefrontal NMDA receptor-mediated transmission. Our data suggest that adjunctive treatment with a NET inhibitor may enhance the therapeutic effect of low-dose olanzapine in schizophrenia without increasing EPS liability and add an antidepressant action, thus in principle allowing for a dose reduction of olanzapine with a concomitant reduction of dose-related side effects, such as EPS and weight gain.
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PMID:Reboxetine enhances the olanzapine-induced antipsychotic-like effect, cortical dopamine outflow and NMDA receptor-mediated transmission. 2046 59