Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current treatment strategies for levodopa-induced psychosis in Parkinson's disease have had limited success. Remoxipride, a selective D2 receptor antagonist, was administered in an open label pilot study to seven parkinsonian patients exhibiting thought disorder. Symptoms improved significantly in six patients after treatment durations of 1-6 months and cleared completely in two individuals. One patient (at age 90 the oldest in the group) could not tolerate the compound due to significant motor deterioration, and the drug had to be discontinued after 1 week. In all remaining patients, no motor complications appeared, and therapeutic effects of remoxipride continued for up to 3 months after treatment cessation and have lasted for 2 years now in one individual. Further study of this compound in the context of treatment-induced psychosis in Parkinson's disease appears to be warranted.
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PMID:Symptomatic relief from treatment-induced psychosis in Parkinson's disease: an open-label pilot study with remoxipride. 819 83

Remoxipride is a novel substituted benzamide that more effectively blocks mesolimbic than striatal D2 dopamine receptors. We used remoxipride in the management of nine patients with Parkinson's disease (PD) who were experiencing visual hallucinations due to dopaminergic therapy. Remoxipride was begun in a dose of 25 mg three times daily and gradually increased to 75-225 mg/d (mean 161 mg). The psychiatric status improved in eight patients. Little or no change in the severity of parkinsonism was noted in five, a mild increase in two, and a moderate increase in two. Because one patient with moderately severe levodopa-induced dyskinesias experienced a reduction in the abnormal movements without a substantial increase in parkinsonism, we began a trial of remoxipride for disabling peak-dose dyskinesias. The trial was abandoned after every one of the first four patients entered experienced an immediate, severe, and prolonged increase in off periods with single 10- to 25-mg doses. This striking differential response to an atypical neuroleptic with weak striatal D2 antagonist properties indicates that different states of postsynaptic dopamine receptor sensitivity or synaptic dopamine levels may be associated with various disease- and treatment-related problems found in late-stage PD.
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PMID:Remoxipride in Parkinson's disease: differential response in patients with dyskinesias fluctuations versus psychosis. 866 33

Levodopa-induced psychotic symptoms frequently complicate the management of patients with Parkinson's disease (PD). We examined the efficacy and tolerability of a novel antipsychotic, remoxipride, in this population. This was a 7-week, open-label pilot evaluation of patients with moderate to severe PD and levodopa-induced psychotic symptoms of at least 2 months' duration. The patients were recruited at the Movement Disorders Clinic, The Toronto Hospital, a tertiary referral center. After 1 week of baseline observation, the patients received remoxipride, 25 mg, three times a day orally, with the dose increasing by 25 to 50 mg each week as tolerated. The outcome measures included the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impressions (CGI) scale, and the United Parkinson's Disease Rating Scale. Adverse symptoms were elicited by an open-ended questionnaire and a symptom checklist. Six men and three women aged 69.3 +/- 9 years received remoxipride 147 +/- 57 mg/day. Total BPRS score decreased modestly in eight of nine subjects, and there was a statistically significant improvement of mental status as indicated by the CGI scale score, which decreased from 3.8 +/- 0.4 at baseline to 2.4 +/- 1.3 at last rating (p < 0.05; Wilcoxon signed rank test). The motor performance deteriorated somewhat in two subjects, whereas the rest showed no appreciable change. The most common adverse effects included tremor, rigidity, akathisia, and hypersalivation. Remoxipride treatment reduced psychotic symptoms in eight of nine subjects while having no appreciable effect on the parkinsonian status of seven of nine subjects.
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PMID:Remoxipride in the treatment of levodopa-induced psychosis. 888 13

To clarify the role of dopamine D1 and D2 receptors in the volume-induced micturition reflex, conscious, female rats were investigated cystometrically before and after intravenous administration of SKF 38393 (a selective D1 receptor agonist), SCH 23390 (a selective D1 receptor antagonist), quinpirole (a selective D2 receptor agonist), and remoxipride (a selective D2 receptor antagonist). The effect of quinpirole was also investigated in the presence of remoxipride. Intravenous administration of SKF 38393 (0.01-3.0 mg/kg) did not affect any cystometric parameters investigated. On the other hand, SCH 23390 (0.1-1.0 mg/kg i.v.) reduced bladder capacity and micturition volumes and increased the micturition pressure in a dose-dependent manner. Quinpirole (0.01-0.1 mg/kg) given intravenously, dose-dependently decreased bladder capacity and micturition volumes. Pre-treatment with remoxipride (1.0 mg/kg i.v.) significantly attenuated the effect of quinpirole (0.1 mg/kg i.v.). Remoxipride (0.1-1.0 mg i.v.) itself did not cause any significant changes in the cystometric parameters. These results suggest that in conscious rats, D1 receptors tonically inhibit the micturition reflex and that D2 receptors are involved in facilitation of the micturition reflex. It may be speculated that detrusor hyperreflexia associated with Parkinson's disease results from activation failure of D1 receptors and that administration of D2 receptor agonists might worsen the condition.
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PMID:Role of dopamine D1 and D2 receptors in the micturition reflex in conscious rats. 1113 87