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)

Psychosis secondary to dopaminergic therapy can limit the ability to manage motor symptoms of advanced Parkinson's disease (PD). We report the results of an open label 3-month trial that evaluated the antipsychotic effects of clozapine in eight PD patients with drug-induced psychosis. Response was quantified using a simplified brief psychiatric rating scale and two PD scales. Clozapine significantly improved psychiatric scores at low doses. The use of every other day regimens (not previously utilized) led to good control of symptoms and minimized side effects. Clozapine also had a positive sleep effect in four patients and improved dyskinesia in one. Finally, this treatment prevented recurrence of psychosis while levodopa doses were significantly increased and while other antiparkinsonian medications were added. Motor disability related to PD improved as a result of these treatment adjustments. We conclude that clozapine is effective in treating drug-induced psychosis in PD and allows for safe optimization of antiparkinsonian therapy.
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PMID:Clozapine prevents recurrence of psychosis in Parkinson's disease. 135 59

Parkinson's disease (PD) is frequently associated with psychiatric problems. Depression generally responds to antidepressant medications or to electroconvulsive therapy (ECT). The nondepressive psychoses generally require a reduction in parkinsonian medications, or possibly a "drug holiday." In patients whose psychosis fails to respond to a reduction in medication or who cannot tolerate the worsening parkinsonism, an antipsychotic drug should be added. Clozapine is probably the drug of choice, with low potency neuroleptics being second-line options.
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PMID:The management of the levodopa psychoses. 168 May 56

Dopamine receptors belong to the family of G protein-coupled receptors. On the basis of the homology between these receptors, three different dopamine receptors (D1, D2, D3) have been cloned. Dopamine receptors are primary targets for drugs used in the treatment of psychomotor disorders such as Parkinson's disease and schizophrenia. In the management of socially withdrawn and treatment-resistant schizophrenics, clozapine is one of the most favoured antipsychotics because it does not cause tardive dyskinesia. Clozapine, however, has dissociation constants for binding to D2 and D3 that are 4 to 30 times the therapeutic free concentration of clozapine in plasma water. This observation suggests the existence of other types of dopamine receptors which are more sensitive to clozapine. Here we report the cloning of a gene that encodes such a receptor (D4). The D4 receptor gene has high homology to the human dopamine D2 and D3 receptor genes. The pharmacological characteristics of this receptor resembles that of the D2 and D3 receptors, but its affinity for clozapine is one order of magnitude higher. Recognition and characterization of this clozapine neuroleptic site may prove useful in the design of new types of drugs.
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PMID:Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. 184 Jun 45

Clozapine (CLOZ) is an atypical antipsychotic drug being used with increasing frequency throughout the world and has recently been commercially marketed in the United States. Its unique properties make it a promising but challenging drug to use in the treatment of schizophrenia. In order to use CLOZ most effectively and efficiently, clinicians must be aware of its potential benefits and risks. This report is a review and critical evaluation of current knowledge regarding the clinical efficacy and side effects of CLOZ. Although CLOZ has proven to be effective in some treatment-refractory schizophrenic patients and to produce relatively few extrapyramidal side effects compared to classical neuroleptic drugs, several issues require further investigation including what defines neuroleptic intolerance, the optimal dose range, and the appropriate duration of a CLOZ treatment trial. Similarly, studies are needed to determine what role CLOZ should have in the treatment of patients with predominantly negative symptoms and those patients who are only partially responsive to standard neuroleptics. In addition, important questions remain as to what other conditions might be indications for CLOZ, for example, schizoaffective disorder, affective psychoses, and idiopathic Parkinson's disease.
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PMID:Update on the clinical efficacy and side effects of clozapine. 188 9

Clozapine is an atypical neuroleptic medication that is free of parkinsonian side effects and that has been reported to ameliorate the tremor of Parkinson's disease. We report (with videotape illustration) the dramatic improvement of severe yet classic rest tremors in one elderly nonpsychotic patient with Parkinson's disease and significant improvement in four others. We believe that clozapine, in low doses, may be a useful medication for the treatment of rest tremor in Parkinson's disease, even in cases without mental abnormalities.
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PMID:Clozapine-responsive tremor in Parkinson's disease. 238 38

Clozapine is an antipsychotic medication that is virtually free of extrapyramidal side effects. We report our successful treatment of 6 patients with idiopathic Parkinson's disease and various psychoses using clozapine on a chronic basis along with carbidopa/L-dopa.
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PMID:Clozapine in the treatment of psychosis in Parkinson's disease. 239 40

Initiating treatment in a patient with Parkinson's disease requires consideration of age, degree of disease activity, and consequences of long-term treatment. In young patients, albeit dopaminergic agonists or selegiline are possible alternatives, they will never be as effective as L-dopa, and they can be used only initially in very mild cases and for a short period of time. Long-acting L-dopa is probably better after titration with standard preparations. Potential neuroprotection by selegiline has not been confirmed so far, but it acts as a mild anti-Parkinsonian. In patients over 60, it is recommended not to use anticholinergic or dopaminergic agonists, but to start with a low dose of L-dopa and increase it by a maximum of 125 mg every 7 to 10 days. Clozapine can be very useful against psychosis.
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PMID:[Initiation of treatment in Parkinson disease]. 748 Dec 98

Recent research on the role of clozapine in the treatment of Parkinson's disease and other movement disorders is discussed. Most clinical trials have shown resolution of or improvement in psychotic symptoms accompanying Parkinson's disease without worsening of parkinsonian symptoms. Adverse effects appear to be mild at dosages of < 100 mg/day; sedation is the most frequent problem. Most of these studies have serious limitations, however; until better studies have been completed, the decision to use clozapine for Parkinson's disease-related psychosis should be made on a case-by-case basis, with thorough evaluation of risks, benefits, and other therapeutic options. Some patients with Parkinson's disease have shown improvement in tremor and other abnormal movements when given clozapine. Clozapine cannot be recommended for treating tardive dyskinesia on the basis of the research done so far; some trials show dramatic resolution of symptoms, others no benefit. Anticholinergics or dopamine-reuptake inhibitors should be considered before clozapine is given to patients with tardive dyskinesia because of clozapine's potential for serious adverse effects. A few patients with Huntington's disease have responded to clozapine, but again no conclusions can be drawn. Clozapine appears to offer no real advantage over haloperidol for treating choreiform movements in Huntington's disease. The frequency of tics in Tourette's syndrome does not seem to be reduced by clozapine. Clozapine has shown some efficacy as a treatment for psychosis and abnormal movements in Parkinson's disease. Results have been less promising for other movement disorders. Further study in larger populations is needed before any definitive conclusions about clozapine's place in movement disorder therapy can be made.
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PMID:Clozapine therapy for Parkinson's disease and other movement disorders. 853 51

Delusions and other manifestations of psychotic behavior are common side effects in Parkinson's disease (PD) patients chronically treated with dopaminergic drugs. Clozapine, a dibenzodiazepine derivative, is an antipsychotic drug largely devoid of extrapyramidal side effects. We evaluated the effects of low doses of clozapine on the mental and motor functions in PD patients requiring antipsychotic treatment. Twenty-seven PD patients taking dopaminergic drugs and who had psychotic behavior received clozapine at 12.5 to 75 mg/d. Fifteen patients received clozapine for 1 to 11 months (mean, 6.8 months) and seven received it for 12 to 24 months (mean, 18 months). No patient exhibited motor deterioration, and the psychotic features disappeared immediately, allowing discontinuation of clozapine after several months in 10 patients. Fifteen patients are still receiving clozapine and are free of psychiatric symptoms. The clozapine treatment was discontinued after 5 days (25 mg/d) in two patients because of somnolence. No patient developed neutropenia. Clozapine in low doses is effective in the treatment of drug-induced delusions and hallucinations in PD.
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PMID:Low-dose clozapine in the treatment of levodopa-induced mental disturbances in Parkinson's disease. 789 90

This article reviews new medical and surgical treatments for Parkinson's disease (PD). Catechol-O-methyl-transferase (COMT) inhibitors supplement the variety of antiparkinsonian drugs interacting with the dopaminergic system. Clinical studies show that COMT inhibitors prolong the action of levodopa in patients with the "wearing off" phenomenon. The atypical antipsychotic drug clozapine is the treatment of choice for the alleviation of levodopa-induced psychosis. Clozapine also has beneficial effects on tremor and levodopa-induced dyskinesias. Thus, COMT inhibitors and clozapine provide new opportunities for the treatment of patients with longstanding PD and fluctuating responses to levodopa. Experimental evidence in animals suggests that glutamate antagonists have symptomatic and neuroprotective actions in PD. At present, however, only weak antiglutamatergic drugs that have low specificity, such as memantine, amantadine, and budipine are available for clinical studies. Neurotrophic factors, in particular ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, are among the most promising new approaches for neuroprotection in PD. Problems of bioavailability, however, thus far preclude their use in patients. An improved understanding of the pathophysiology of parkinsonism has led to a renaissance of stereotaxic surgery. The subthalamic nucleus is a potential new target for surgical intervention. Ventroposterior pallidotomy has been shown to improve not only rigidity and tremor, but also akinesia. The techniques for thalamic interventions have been refined by introducing chronic thalamic stimulation. Future transplantation approaches to PD will focus on the use of genetically modified cells carrying genes for dopamine-synthesizing enzymes or neurotrophic factors. Animal studies show the feasibility of in vivo gene transfer for the treatment of PD.
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PMID:New medical and surgical treatments for Parkinson's disease. 795 44


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