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)

Dysfunction of dopamine neural systems is hypothesized to underlie neuropsychiatric disorders and psychostimulant drug abuse. At least three dopamine systems have been characterized in the brain-nigrostriatal, mesolimbic, and mesocortical. Abnormalities of nigrostriatal dopamine neurons cause motor impairment leading to Parkinson's disease, whereas dysfunction of mesolimbic and mesocortical dopamine neurons are most implicated in psychotic disorders such as schizophrenia and in drug addition. One of the primary neural sites of action of potent antipsychotic agents and psychostimulant drugs of abuse are dopamine receptors and dopamine transporters which, respectively, mediate the induction and termination of dopamine's actions. Very limited information is, however, available about which particular set of dopaminergic cells in the human brain actually express the genes for these dopamine-specific proteins. In this study, we observed that the dopamine transporter and D2 receptor messenger RNAs are differentially expressed within the human mesencephalon: highest expression in ventral subpopulations of the substantia nigra pars compacta neurons with lowest expression in the mesolimbic/mesocortical ventral tegmental area and retrorubral cell groups. These findings suggest that motor- and limbic-related mesencephalic neurons in the human brain differ in the degree of dopamine transporter and D2 receptor gene expression.
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PMID:The dopamine transporter and dopamine D2 receptor messenger RNAs are differentially expressed in limbic- and motor-related subpopulations of human mesencephalic neurons. 789 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

In the first section of this paper several aspects of tardive dyskinesia (TD) (clinical, epidemiological, pharmacological) are reviewed. We propose that this syndrome is not the consequence of dopamine receptor proliferation, but results from damage or degeneration of striatal cholinergic interneurons. We suggest that this cellular damage is caused by prolonged overactivation of these neurons, which occurs when they are released from dopaminergic inhibition following neuroleptic administration. Overactivity of central cholinergic systems during akinetic and motor retarded depression could be a contributory cause. The predisposition to L-DOPA-induced peak-dose dyskinesia in Parkinson's disease may depend on the same type of striatal neuronal loss. In the second part of the paper, the subject of supersensitivity psychosis and drug-resistant schizophrenia is reviewed. These two syndromes, are commonly associated with TD, have similar predisposing factors and pharmacology to TD, and are potentially persistent. We suggest that these conditions also result from degeneration of cholinergic striatal interneurons following chronic neuroleptic administration. The efficacy of clozapine for such treatment-refractory psychoses is explained in terms of its blockade of D-1 dopamine receptors. Other drugs effective against refractory psychoses (e.g. risperidone) are predicted to reduce activation at D-1 receptors.
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PMID:Loss of striatal cholinergic neurons as a basis for tardive and L-dopa-induced dyskinesias, neuroleptic-induced supersensitivity psychosis and refractory schizophrenia. 790 33

We report the case of a 49-year-old woman with a therapy resistant paranoid hallucinatory psychosis and coexisting severe symptoms of Parkinson's disease. Over a 3-week period she received electroconvulsive therapy (ECT) 10 times, while the medication of haloperidol 8 mg/day, thioridazin 90 mg/day, metixen 17.5 mg/day and biperiden 6 mg/day was continued. There was a general improvement of the clinical picture, more pronounced for the parkinson symptomatology than for the psychotic disorder.
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PMID:[Electroconvulsive therapy in comorbidity of treatment refractory paranoid hallucinatory psychoses with Parkinson disease]. 790 17

Neuroleptic malignant syndrome (NMS) was first recognized as a life-threatening complication of dopamine receptor antagonists characterized by extrapyramidal disturbances, hyperthermia, and elevated serum creatine kinase levels. Concepts of NMS have changed because medications other than classic neuroleptic drugs have been implicated as triggering agents and because syndromes identical to NMS have been observed in patients with Parkinson's disease withdrawn from their medication or suffering akinetic hyperthermic parkinsonian crisis. The neurochemical key features in all these conditions are probably functional dopamine deficiency and ensuing hyperactivity of excitatory amino acid neurotransmission in the basal ganglia and hypothalamus. Recognition of NMS is the most important step in its management; the outcome is good if causative drugs are discontinued or if parkinsonian therapy is readjusted. Supportive care includes management of hyperthermia and fluid replacement. Controversial therapeutic measures include the application of dopamine receptor agonists, excitatory amino acid antagonists, or dantrolene. Psychiatric patients with a history of NMS and psychotic relapse necessitating neuroleptic drugs do not commonly redevelop NMS when reexposed to dopamine receptor antagonists but may be treated most safely with atypical neuroleptic drugs such as clozapine.
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PMID:Neuroleptic malignant syndrome. 795 45

We compared the efficacy and safety of pergolide and bromocriptine in 57 patients with Parkinson's disease (PD) with a declining response to levodopa therapy in a single-blind, crossover study. Patients were placed randomly on the sequence bromocriptine-pergolide (12 + 12 weeks) or vice versa. Regular evaluations using the New York University Parkinson's Disease Scale were performed by a clinician blinded to treatment assignment. Patients' and clinicians' impressions also were recorded. The average daily dose of pergolide was 2.3 +/0- 0.8 mg, and that of bromocriptine was 24.2 +/- 8.4 mg. Significantly greater efficacy was demonstrated by both drugs as adjunctive therapy to levodopa compared with previous treatment of levodopa alone (pergolide, p = 0.0001; bromocriptine, p = 0.0005; Wilcoxon t test). Pergolide was more effective than bromocriptine in daily living scores (p = 0.020) and motor scores (p = 0.038). No difference in dyskinesias, dystonias, and psychosis was observed. Adverse events were more frequent in bromocriptine-treated patients. Most patients and physicians preferred pergolide to bromocriptine. Pergolide as adjunctive therapy to levodopa was more effective than bromocriptine in this short-term trial.
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PMID:Pergolide compared with bromocriptine in Parkinson's disease: a multicenter, crossover, controlled study. 796 10

Recent findings in monkeys indicate that excitatory amino acids such as glutamate are involved in the pathophysiological cascade of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)- induced neuronal cell death. The neuroprotective effects of competitive and non-competitive NMDA (N-methyl-D-aspartate) antagonists against MPTP toxicity support the hypothesis that NMDA receptor-mediated events are involved in the neurotoxicity of MPTP. These results suggest that the clinical trial of NMDA antagonists in patients with Parkinson's disease should be performed. Further evidence obtained in animal models of Parkinson's disease indicates that both competitive NMDA antagonists and AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) antagonists show symptomatic anti-parkinsonian activity in combination with L-DOPA. Glutamate antagonists may therefore retard the progression and improve the symptomatology of Parkinson's disease. The 1-amino-adamantanes amantadine and memantine have recently been shown to be non-competitive NMDA antagonists and are widely used in Europe as anti-parkinsonian agents. Both compounds are likely to cause pharmacotoxic psychosis as an unwanted side-effect. Clinical trials are needed to test the efficacy of the 1-amino-adamantanes with respect to the progression of Parkinson's disease.
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PMID:Glutamatergic drugs in Parkinson's disease. 799 66

Apomorphine is a potent dopamine agonist at both D1 and D2 receptors and has been used successfully for treating the 'on/off' phenomenon in Parkinson's disease. We report our experience with apomorphine in treating the 'on/off' phenomenon in L-dopa responsive idiopathic Parkinson's disease. Thirteen such patients were commenced on apomorphine infusions. Their mean age was 69 (range 53-80) years and the mean duration of the disease was 15 (range 6-28) years. The clinical response to apomorphine was good in four patients, fair in two, unchanged in five and worse in two. Activities of daily living improved in six, were unchanged in five and worse in two. When the response was poor or showed no change, apomorphine was discontinued. In addition, apomorphine was also discontinued in three patients who had had a fair/good response but suffered side effects of hallucinations, delusions and psychosis, lack of cooperation or found the pump inconvenient. Apomorphine was continued in only three patients out of 13.
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PMID:Subcutaneous apomorphine infusion in Parkinson's disease: does it have a role? 801 4

Of 261 patients with clinically diagnosed Parkinson's disease (PD), whose age at the onset was 58.2 +/- 11.3, 46 patients with the onset age above 70 (the mean for the whole group + 1SD) were compared to 44 patients with onset age below 47 (the mean for the whole group - 1 SD). Old-onset PD patient were more susceptible to develop psychotic complications of levodopa treatment. More often had they tremor both as presenting and dominant symptom of their disease. Among young-onset PD bradykinesia was more often the dominant clinical feature, and susceptibility to levodopa induced dyskinesia was higher. In 9 cases of young-onset PD (20.5% of this group) paraesthesia was a presenting symptom, compared to only 1 patient (2%) in the group of old-onset PD.
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PMID:Old-onset Parkinson's disease compared with young-onset disease: clinical differences and similarities. 804 42

Risk factors of Parkinson's disease (PD) were studied by the case-control method (1:1) in 90 cases. It was suggested that the high positive rate (34.4%) in PD family history was related to "genetic susceptibility". There was history of head injury, rheumatic fever, seizure, taking anti-psychosis drug or contact with toxins, but any one factor could not completely explain the etiology of PD. We believe that coordinating effects of both susceptibility in genetics and environmental toxins may explain the mechanism of PD.
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PMID:[A case-control study on risk factors in etiology of Parkinson's disease]. 808 43


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