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)

The nicotinic cholinergic amine piperidine diminished both the dyskinesia and the symptomatic control in some patients with Parkinson disease receiving levodopa. Since the piperdine configuration is contained in the molecules of the apomorphine and N-propylnoraporphine, it might be responsible for the antagonism of these drugs to some effects of levodopa in Parkinson disease and for the palliation by apomorphine of some dopamine-mediated symptoms in other extrapyramidal disorders.
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PMID:Antagonism by piperidine of levodopa effects in Parkinson disease. 56 44

In 19 patients with Parkinson disease, we studied the relationship of the therapeutic effect of levodopa, or dyskinesia, to the plasma content of DOPA and growth hormone (GH). Those with stable responses to levodopa, individually or as a group, showed stable and lower plasma DOPA levels than those with unstable symptomatic responses. These results show that stable and oscillating clinical responses in Parkinson disease parallel plasma DOPA levels, suggesting that there are different mechanisms in peripheral levodopa metabolism and that extracerebral mechanisms are important in regulating the availability of levodopa to the brain. Plasma GH did not differ in the two groups, suggesting that the secretion of GH is independent of the effects of levodopa in parkinsonism.
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PMID:Plasma DOPA and growth hormone in parkinsonism: oscillations in symptoms. 57 Oct 63

It has been suggested that patients with Parkinson disease partially compensate for neuron loss by developing denervation supersensitivity, and, if so, that prolonged levodopa (L-dopa) therapy might lead to desensitization. As a preliminary test of this hypothesis, and in order to study whether it was possible to "resensitize" a patient who had already presumably been desensitized by previous L-dopa therapy, a patient who had become unpredictably responsive to L-dopa was investigated. The patient had been taking L-dopa for eight years and had exhibited severe dyskinesia-akinesia oscillation ("on-off" phenomenon) before the study. There was no consistent response to his hourly doses of Prolopa (L-dopa and benserazide in a 4:1 ratio). He was first lowered, over 33 days, to 20% of his original Prolopa dose. The dosage was then increased until a consistent response was observed. The three main results achieved were, first, overall reduction by 64% of the daily requirement for L-dopa; second, conversion from a previously unpredictable to a predictable response to each dose of L-dopa; and, third, change in his movement fluctuations to a pattern more typical of "end-of-dose" akinesia than the "on-off" phenomenon. The results support the idea of dopamine receptor resensitization upon reduction of the L-dopa dosage.
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PMID:The L-dopa on-off effect in Parkinson disease: treatment by transient drug withdrawal and dopamine receptor resensitization. 74 58

The broad results of the treatment of patients with idiopathic Parkinson's disease who have received levodopa or its variants are reported. 50 patients, 24 males and 26 females, with a mean age of 66.5 years were treated with levodopa, in daily doses ranging from 0.25g to 6.0g or 'Sinemet' in daily doses of 300mg to 750mg. Periods of treatment ranged from 4 months to 8 years, with a mean of 4.02 years. The relationships of patients' age, onset of Parkinsonian symptoms and interval between initial treatment with levodopa and the current clinical state were studied. Patients were classified according to their clnical response into 3 categories: satisfactory response, progressive deterioration or intolerance of levodopa. The proportion of patients in each category was 66%, 22% and 12% respectively. The clinical results of treatment correlated with those of Webster Disability Testing Scale. Analysis showed that the majority of patients tolerated levodopa and showed an initially satisfactory response. Patients who responded well were considerably younger than those who failed to respond. Patients receiving the drug for a shorter period (less than 3 years) showed a better response. After 3 years' treatment, the response declined. Patients who had had Parkinson's disease for more than 4 years appeared to do less well than those with recently diagnosed disease, but many patients responded well even when treatment was initiated 10 years after the onset of symptoms. Patients discontinued levodopa treatment because of psychoses, nausea, dyskinesia or exacerbation of urinary incontinence. The commonest side effects were nausea (34%), postural hypotension (22%), psychoses (10%) and 'on-off' phenomena in 12% of patients.
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PMID:Patterns of response to levodopa in Parkinson's disease. 75 20

The authors describe the results of biochemical analysis carried out on 28 patients with Parkinson's disease who had been treated by L-dopa. Twenty of them showed either no abnormal movements at all or very few, eight others had considerable dyskinesia. Biochemical analysis of the urinary degradation products of L-Dopa revealed the existence of a swing in the degradation of dopamine towards 4-O-methylate derivatives in dyskinetic patients (significant difference at .01). The results confirm those obtained in their initial analysis carried out in 1973. The authors express the view that abnormal movements while under L-Dopa treatment are dependent on two factors: one, the hypersensitivity of dopaminergic reception, the other, the greater or lesser preponderance of the COMT isozyme giving rise to 4-O-methylates;
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PMID:[Abnormal movements of patients with Parkinsonism treated with L-dopa and anomalies of dopamine metabolism]. 84 19

Forty patients have been treated with Sinemet (L-carbidopa/L-dopa) for a period of up to two years. The results are in agreement with those in the literature. In two-thirds of cases a good to very good improvement was obtained. The principal side effects were dyskinesia, hypotonia, and gastrointestinal and psychotic symptoms, though they seldom necessitated treatment interruption. L-carbidopa/L-dopa affords a real alternative therapy in the modern treatment of Parkinson's disease with L-dopa and a decarboxylase inhibitor. Generally the dosage range was up to a maximum of one tablet three times daily. Sinemet tablets are simple and convenient to handle for both doctor and patient. Dosage titration to therapeutic efficacy can be achieved in one week to ten days without complications, though we recommended a slower titration based on individual patient reaction and requirements.
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PMID:[Treatment of Parkinson's disease with the combination drug L-carbidopa/L-dopa. Report on a 2 years study]. 84 50

The author analyzes parkinsonism and hyperkinesia in psychiatric patients with tardive dyskinesia before and during treatment with alpha-methyl-p-tyrosine (AMPT, a dopamine antagonist), biperiden (an acetylcholine antagonist), and baclofen (a GABA agonist); and in patients with paralysis agitans and L-dopa-induced hyperkinesia. AMPT and baclofen had similar influences on oral dyskinesia, resulting in reduced frequency, unchanged or slightly reduced amplitude, and increased duration of each movement. The author concludes that: 1) reduced dopaminergic activity may be the primary pathogenetic background for tardive dyskinesia; 2) dopaminergic hypersensitivity and/or cholinergic hypofunction is necessary before hyperkinesia breaks through; and 3) the neurotoxic effects of neuroleptics may be associated with age-dependent changes in nigrostriatal regions representing oral innervation.
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PMID:The relationship between parkinsonism and tardive dyskinesia. 86 56

The authors, by describing their own observations made on eight patients showing extrapyramidal syndromes as side effects of metoclopramide (Cerucal) medication, report the various kinds of possible side effects, discussing their conformity with side effects produced by conventional neuroleptics and showing methods of treatment. Metoclopramide is known to produce three froms of extrapyramidal and motor side effects, namely: 1. Dyskinetic syndrome; 2. acathisia; and 3. Parkinson's syndrome. Therapy is in the following form regardless of the particular side effect produced by the said drug: 1. Administration of antiparkinsonian remedies; 2. administration of coffein; and 3. discontinuation or drastic reduction, respectively, of the daily dose of Cerucal.
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PMID:[Extrapyramidal syndromes as side-effects of metoclopramide (Cerucal) medication]. 101 73

To avoid the main drawbacks of prolonged treatment with levodopa (involuntary movements and the "on-off" phenomenon), we administered apomorphine by mouth to 14 patients with Parkinson's disease. This treatment caused azotemia, which we circumvented by switching to N-propylnoraporpine, whose nephrotoxic dose (80 mg six times per day) was larger than its therapeutic dose (10 to 15 mg six times per day). Slowly increasing doses induced significant improvement (P less than 0.005) in all 24 patients studied, transitory mental aberrations in seven, and release of growth hormone in three patients tested. In patients previously on prolonged levodopa administration, the dyskinesia and "on-off" phenomenon were almost identical with N-propylnoraporphine, but both drawbacks were reduced or abolished in six patients by coadministration of alpha-methyldopa hydrazine plus levodopa. This coadministration seemed to abolish tachyphylaxis. We conclude that N-propylnoraporphine is very useful in the treatment of Parkinson's disease.
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PMID:Treatment of Parkinson's disease with aporphines. Possible role of growth hormone. 110 35

Irregularities in motor response after continuing levodopa therapy of Parkinson disease (the "on-off effect") were assessed with the addition of L-alpha-methyldopa hydrazine (carbidopa) in a double-blind study. Thirteen of 20 patients improved while receiving carbidopa and levodopa while only four of 17 patients improved while receiving placebo and levodopa. Twenty-three of 37 patients improved in a subsequent non-blind trial of carbidopa plus levodopa. Improvement was not dependent on an increase in dose or frequency of levodopa administration. Adverse effects included dyskinesia, imbalance, and confusion; nausea was eliminated. On patient died of glomerulonephritis that predated the drug trial, but worsened progressively during and after it. Carbidopa's suppression of the "on-off effect" suggests that extracerbral factors may be important in this phenomenon.
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PMID:Treatment of "on-off effect" with a dopa decarboxylase inhibitor. 115 14


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