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

The plasma amine oxidase (benzylamine oxidase, BzAO) of patients with Parkinson's disease is sometimes decreased in activity, when compared to normal controls. This is the result of therapy with DOPA decarboxylase inhibitors. The Authors suggest that complications due to prolonged therapy with these drugs may be, at least in part, the result of an interference with BzAO capacity to catabolize circulating amines.
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PMID:Inhibitory effect of drugs used in the treatment of Parkinson's disease on plasma monoamine oxidase activity. 398 25

Brocresine, an aromatic L-amino acid decarboxylase inhibitor with both a peripheral and central action was shown to potentiate the therapeutic effect of levodopa in Parkinson's disease. The search for useful decarboxylase inhibitors therefore need not be limited to agents that do not pass the blood/brain barrier.
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PMID:Brocresine in Parkinson's disease. Action of a peripheral and central decarboxylase inhibitor in potentiating levodopa. 457 Sep 3

Thirty patients with Parkinson's disease were treated for four weeks with levodopa combined with an inhibitor of extracerebral dopa decarboxylase, L-alpha-methyldopahydrazine (MK 486). The therapeutic results were compared with the effects of treatment of a group of 40 patients with levodopa alone. Patients treated with the combined therapy improved more rapidly, had less nausea and vomiting, and required a much smaller dose of levodopa than patients treated with levodopa by itself.
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PMID:Treatment of Parkinson's disease with levodopa combined with L-alpha-methyldopahydrazine, an inhibitor of extracerebral DOPA decarboxylase. 469 82

Human erythrocytes have been found to contain appreciable amounts of DOPA decarboxylase (EC 4.1.1.26) activity. The enzyme activity in erythrocytes from patients with Parkinson's disease who were treated with DOPA was significantly lower than that of untreated patients and of normal individuals. Administration of the drug to mice led to a marked decrease of DOPA decarboxylase in liver and kidney, but not of the brain enzyme. The findings thus indicate that administration of DOPA leads to a decrease in peripheral DOPA decarboxylase, an effect that is expected to be of benefit in DOPA therapy of patients with Parkinson's disease. Peripheral DOPA decarboxylase concentration also decreases in mice after short periods of fasting; the findings suggest that the peripheral enzyme activities may be affected by various nutritional and perhaps hormonal influences, which may be partially responsible for the observed fluctuations in the motor abilities of Parkinsonian patients receiving constant doses of the drug. Study of DOPA decarboxylase activity in erythrocytes may be useful in following changes in patients receiving DOPA therapy and may also be of general interest and value in investigations of catecholamine metabolism in man.
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PMID:Decrease of the 3,4-dihydroxyphenylalanine (DOPA) decarboxylase activities in human erythrocytes and mouse tissues after administration of DOPA. 528 72

The activity of L-dopa decarboxylase was greatly reduced in the striatum, less so in the hypothalamus, and unchanged in the cortex of brains of patients with Parkinson's disease. However, it appears that even in the striatum enough activity remained to allow for the formation of dopamine from L-dopa in patients treated with large doses of L-dopa.
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PMID:Parkinson's disease: activity of L-dopa decarboxylase in discrete brain regions. 547 94

In parkinsonian brain, TH and the BP cofactor, as well as DBH and PNMT with phenylethanolamine as substrate, are decreased. However, decrease in AADC with L-DOPA as substrate was not statistically significant. TH activity has also been shown to be decreased in striatonigral degeneration and Shy-Drager syndrome. TH reduction only in striatum but not in substantia nigra was found in a case of juvenile Parkinson's disease. Changes in AADC with L-DOPA or L-5-HTP as substrates varied in parkinsonian brains. PNMT with norepinephrine as substrate was also significantly decreased in parkinsonian brains. After administration of tyrosine to mice, the BP concentration was increased in striatum, adrenals, and serum. Mean BP concentration in serum of parkinsonian patients was slightly but significantly lower than that in controls. The serum BP increased three- to sevenfold in response to an oral tyrosine load in controls, whereas there was no increase or only a minor one (less than threefold) in parkinsonian patients. Our present results indicate that all catecholamine-synthesizing enzymes and BP synthesis may be impaired in Parkinson's disease.
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PMID:Catecholamine-related enzymes and the biopterin cofactor in Parkinson's disease and related extrapyramidal diseases. 614 12

In intact striatum, the enzyme dopa decarboxylase is localized predominantly in dopaminergic nerve terminals. In Parkinson disease, loss of dopaminergic neurons is associated with massive depletion of striatal decarboxylase activity. Nevertheless, efficacy of exogenous L-dopa in parkinsonism is generally believed to result from its enzymatic decarboxylation to dopamine in the corpus striatum. It has previously been suggested that, after degeneration of nigrostriatal pathways, decarboxylation of administered L-dopa may occur mainly at such striatal sites as surviving dopaminergic terminals, serotonergic neurons, or capillaries; but currently available data do not favor these hypotheses. Recent experimental studies indicate that a substantial amount of decarboxylase activity is localized in striatal interneurons or efferent neurons that may not normally synthesize monoamines. We propose that after depletion of dopaminergic terminals, these nonaminergic striatal neurons may contain a large fraction of residual dopa decarboxylase activity and may represent an important locus for conversion of administered dopa to functional dopamine in the parkinsonian corpus striatum.
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PMID:Nonaminergic striatal neurons convert exogenous L-dopa to dopamine in parkinsonism. 626 9

Forty-four previously untreated patients with early idiopathic Parkinson's disease were treated from the time of diagnosis with submaximum doses of levodopa (mean 420 mg) in combination with a peripheral dopa decarboxylase inhibitor and followed for a minimum period of 3 years. Forty-one gained initial worthwhile improvement, and 17 achieved a reduction in pretreatment disability scores of more than 50%. After 3 years of sustained therapy, only 14 had completely maintained their initial response, and 12 patients were experiencing end-of-dose deterioration; 13 patients had mild peak-dose dyskinesias, but none developed the on-off phenomenon, hypotonic freezing, or end-of-dose dystonia. Retrospective comparison with patients matched for duration of disease and pretreatment severity who had been given maximum tolerated doses of levodopa (a comparable mean dose of 950 mg) showed that the smaller dose regimen reduces peak-dose dyskinesias but not waning of response or end-of-dose deterioration.
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PMID:Sustained low-dose levodopa therapy in Parkinson's disease: a 3-year follow-up. 685 81

Sixteen days after a unilateral lesion of the ventromedial tegmentum (VMT) of the midbrain, adult cats received an intravenous dose of L-DOPA (20 mg/kg), and the caudate nucleus from each hemisphere was removed at various time intervals thereafter. In the caudate nucleus contralateral, to the VMT lesions, DA levels reached 200% of control values within 15 min, and maintained this elevation for at least 2 hours. DA levels in the caudate nucleus ipsilateral to the VMT lesion were much lower than contralateral values; however, they were much higher than those of non-DOPA treated animals with comparable lesions. DA levels in the caudate nucleus of the lesioned hemisphere were directly related to the remaining DOPA decarboxylase activity. The striatal serotonin concentrations were unchanged after L-DOPA, but an increase in 5-hydroxyindoleacetic acid levels was observed. From these results, we conclude that, (i) in cats with nigrostriatal tract lesions after low doses of L-DOPA comparable to those given to patients with Parkinson's disease, the bulk of the newly formed DA in the caudate nucleus is contained in nigrostriatal neurons, and (ii) there exists an inverse relationship between the ability of the caudate to synthesize DA and the severity of the nigrostriatal tract lesion.
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PMID:Kinetics of L-DOPA metabolism in the caudate nucleus of cats with ventrotegmental lesions. 693 23

Early stage Parkinson's disease may be better left untreated if it does not limit motor function. Once limitation of function is present levodopa-dopa decarboxylase inhibitor combinations are the most effective therapy, although amantadine may be satisfactory for a time in milder cases. The optimal independent roles of the ergot derivatives bromocriptine and pergolide, and the MAOb inhibitor selegiline, are not yet generally agreed although they are accepted as useful in supplementing the effects of levodopa. With prolonged levodopa use various late-stage treatment problems may appear. The pathogenesis of these is poorly understood and no completely satisfactory ways of managing them are available.
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PMID:Treatment of Parkinson's disease. 748 55


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