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)

In Parkinson's disease, the concentration of homovanillic acid (HVA) was reduced in lumbar CSF from patients with idiopathic Parkinsonism (n = 54, P less than 0.05) and post-encephalitic Parkinsonism (n = 19, P less than 0.01). The reduction in the concentrations of 5-hydroxyindolylacetic acid (5-HIAA) was not significant, and there was no alteration in the levels of 4-hydroxy-3-methoxyphenylethylene glycol (MHPG). Treatment with L-dopa increased the concentration of HVA in the CSF (P less than 0.05) but had no effect on the levels of 5-HIAA and MHPG. Carbidopa given in combinations with L-dopa produced similar CSF concentrations of dopa as did L-dopa alone but caused less than half the rise in HVA. Fourteen patients who became functionally independent on treatment with L-dopa had higher 5-HIAA levels than 23 patients who showed no such improvement (P less than 0.001), suggesting that intact 5-hydroxyltryptamine neurones may be important in the therapeutic response to L-dopa. In a variety of movement disorders, the levels of HVA, 5-HIAA, and MHPG were not significantly different from age-matched controls. Treatment with tetrabenazine did not significantly alter the metabolite levels in patients in whom it produced either improvement, or side effects.
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PMID:CSF studies on the relationship between dopamine and 5-hydroxytryptamine in Parkinsonism and other movement disorders. 59 81

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

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

It is widely known that administration of L-Dopa benefits patients with Parkinson's syndrome and combination of this drug with decarboxilase does it to a greater extent. In the present study 20 patients with Parkinson's syndrome received MK 486, a combination of L-Dopa and Carbidopa 10:1 (250 mg of the fomer and 25 mg of the latter). The aim of this study was to evaluate therapeutic activity of this drug combination. It was found that MK 486 is effective for controlling clinical manifestation in Parkinson's syndrome. Although side effects were seen frequently, they diminished or disappeared after time of drug administration.
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PMID:[Treatment of Parkinson's syndrome with a combination of levodopa and carbidopa]. 90 17

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

On the basis of observations of 18 patients the authors evaluated clinically the action of Sinement preparation (Merch, Sharp and Dohme) containing L-dopa 250 mg and carbidopa 25 mg in the treatment of Parkinson's disease. In the evaluation particular attention was given to side effects. Therapeutic results of Sinemet and L-dopa alone were compared in patients receiving these drugs alternatively. The observations of authors indicate that Sinemet gives the same therapeutic results as L-dopa, but in much lower doses and with less frequent side effects. Sinemet, similarly as L-dopa exerts the best effect on bradykinesia and muscular rigidity and less on tremor.
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PMID:[Comparison between results achieved by administering L-dopa and Sinemet in parkinsonism in the light of our records]. 118 52

It is now generally acknowledged that L-Dopa is the therapy of choice for Parkinson's Disease. However, L-Dopa has some short comings: It requires large daily dosage, the therapeutic benefits are achieved only after a delayed onset of 1-2 months, and it has a number of side effects both central and peripheral. In the last few years there has been an intense search for agents that are less toxic, more efficient and more rapidly acting that L-Dopa. The ideal agent has not yet been found. However, a combination therapy with L-Dopa and dopa decarboxylase inhibitors has shown promise. The decarboxylase inhibitors used have a large molecule which does not cross the blood brain barrier. Thus when L-Dopa and the decarboxylase inhibitor are given togehher, peripheral production of dopamine from L-Dopa is inhibited, therefore, rendering L-Dopa more readily and rapidly available for brain metabolism. In the present paper we present the results of the treatment of 50 patients on combined therapy using L-Dopa combined with Carbidopa.
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PMID:L-dopa-carbidopa: combined therapy for the treatment of Parkinson's disease. 125 61

92 patients with Parkinson's disease not previously treated with levodopa were considered as eligible for this triple-blind trial. Patients were allocated at random to treatment with either levodopa + benserazide ratio 4:1 (Madopar) or levodopa + carbidopa ratio 10:1 (Sinemet) using dosage schedules recommended by the manufacturers which they had to adhere to for 6 months. Unless prohibitive side-effects occurred daily maximum dosage of 800 mg levodopa + 200 mg benserazide respectively 1,500 mg levodopa + 150 mg carbidopa were obtained after 6 weeks and 3 weeks, respectively. The effect of the two schedules on the Parkinsonian symptoms were equal and appeared equally fast. The frequency of gastrointestinal side-effects and involuntary movements were significantly higher and more severe for Sinemet than for Madopar. These side effects are usually symptoms of levodopa overdosing, but whether or not a different dosage schedule with Sinemet would have given fewer side-effects without concurrent lower efficacy remains open to speculation. The treatment schedules did not differ with regard to other side-effects and influence on blood pressure. Neither treatment seemed to influence liver function, renal function and hematological parameters in a statistically way.
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PMID:Parkinson's disease treated with Sinemet or Madopar. A controlled multicenter trial. 126 76

Carbohydrate metabolism and insulin secretion were investigated in 26 patients with Parkinson's disease before and during L-dopa treatment. Oral glucose tolerance tests were performed on 13 patients treated with L-dopa alone and on 7 patients treated with L-dopa combined with Carbidopa. Intravenous glucose tolerance tests were performed on additional 6 patients treated with L-dopa alone. Results indicate that chronic L-dopa administration does not modify glucose metabolism. It was observed only a significant decrease of insulin secretion after oral glucose in the early phase (15th day) of treatment with L-dopa alone. This temporary effect may be related to the peripheral conversion of L-dopa to dopamine since insulin secretion during combined therapy was normal. The mechanism by which L-dopa transiently inhibits insulin release is not clear. Perhaps the oral administration of L-dopa alone causes an alteration in some gastrointestinal functions which are involved in the handling of oral glucose.
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PMID:Effects of long-term L-dopa therapy on carbohydrate metabolism in patients with Parkinson's disease. 127 95

In a multicenter study we selected 84 patients with fluctuating Parkinson's disease in order to evaluate the effects of controlled-release Sinemet 50/200 (=CR) versus standard Sinemet 25/100 (=STD) in an open-label 8-week titration period, followed by a double-blind, double-dummy 24-week treatment period. In contrast with previous double-blind studies, the efficacy of Sinemet CR proved to be significantly superior to that of Sinemet-STD according to NYUPDS and NUDS rating scales. This higher efficacy of Sinemet CR was not achieved at the expense of safety and/or tolerability. Actual total daily levodopa dosage in patients treated with Sinemet CR was increased by 33%; however, the plasma level of this dosage is calculated to be similar to that of the previous dosage of Sinemet-STD (bio-availability of Sinemet CR is 71%). Mean numbers of daily doses, off-hours, and off-periods were decreased significantly during Sinemet CR treatment. Although all other variables suggest that the number of on-hours had to be increased, statistical significance could not be reached in this respect.
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PMID:Clinical efficacy of Sinemet CR 50/200 versus Sinemet 25/100 in patients with fluctuating Parkinson's disease. An open, and a double-blind, double-dummy, multicenter treatment evaluation. The Dutch Sinemet CR Study Group. 132 9


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