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)

For many patients with Parkinson disease and levodopa-related motor fluctuations, the latency to onset of action of a single dose of a levodopa preparation may be both long and variable. In an effort to find a more rapidly acting and reliable preparation of levodopa, we therefore studied the efficacy of single doses of an oral solution of 250 mg of levodopa methyl ester (ME) with benserazide, 50 mg and of a molar equivalent dose of dispersible Madopar (DM) (50/200) in 13 patients in the fasting state after overnight drug withdrawal. The response of seven of these patients was compared to that after two Sinemet 25/100. The latency to "on" was equally fast with ME and DM, and significantly faster than after standard Sinemet. The duration of "on" was similar with all three. Because of this more rapid relief of "off" periods, both ME and DM offer a potential clinical advantage over standard preparations of levodopa.
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PMID:The clinical efficacy of single morning doses of levodopa methyl ester: dispersible Madopar and Sinemet plus in Parkinson disease. 147 49

20 patients with Parkinson's disease and a fluctuating response to chronic treatment with conventional L-dopa preparations participated in an open randomized trial comparing two sustained-release L-dopa preparations (Madopar HBS, Sinemet CR4). While a majority (15 patients, 7 on Madopar HBS and 8 on Sinemet CR4) showed a favourable response after 2 months of slow-release L-dopa treatment the clinical benefit remained stable in only 2 patients on Madopar HBS and 3 patients on Sinemet CR4 over the entire follow-up period of 12 months. Reasons for treatment failure were increased peak-dose or biphasic dyskinesias or prolonged "off"-periods. This preliminary study failed to demonstrate clinically significant advantages of one slow-release principle over the other.
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PMID:Comparative efficacy of two oral sustained-release preparations of L-dopa in fluctuating Parkinson's disease. Preliminary findings in 20 patients. 157 Oct 80

We compared the efficacy of a single dose of an oral solution of levodopa methyl ester (ME) to that of standard levodopa, in the form of a single dose of Madopar, in reversing afternoon "off" periods in 12 patients with Parkinson's disease (PD). The highly soluble ME solution led to a significantly more rapid reversal of "off" periods. This preparation may therefore convey a clinical advantage in patients experiencing motor fluctuations whilst taking multiple daily dosages of levodopa, particularly in those with long or highly variable latency to the next "on" period.
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PMID:The clinical efficacy of oral levodopa methyl ester solution in reversing afternoon "off" periods in Parkinson's disease. 207 Mar 64

A random biochemical screening followed by lead optimization culminated in the discovery of Ro 40-7592 3,4-dihydroxy-4'-methyl-5-nitrobenzophenone). Ro 40-7592 was found to inhibit COMT in a competitive fashion both in the CNS and in the periphery (Ki for the liver enzyme = 30 nM). Ro 40-7592 (30 mg/kg p.o.) combined with benserazide (15 mg/kg p.o.) and a low dose of L-DOPA (10 mg/kg p.o.) almost completely blocked (for about 6 h) the formation of 3-O-methyldopa (3-OMD) in brain and plasma, producing a long-lasting increase of L-DOPA in plasma and a parallel marked increase of L-DOPA and dopamine in the brain. Ro 40-7592, combined with peripheral decarboxylase inhibitors and L-DOPA (as in Madopar and Sinemet), will offer substantial advantages in the therapy of Parkinson's disease, i.e. enhanced bioavailability and prolonged plasma half-life of L-DOPA, pronounced DOPA sparing effect and blockade of 3-OMD formation.
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PMID:Ro 40-7592: inhibition of COMT in rat brain and extracerebral tissues. 208 2

In five levodopa (L-dopa)-treated patients with Parkinson's disease with severe fluctuations of motor performance, plasma L-dopa as well as dopamine levels were measured during 2 days, first under optimal standard L-dopa with peripheral decarboxylase inhibitor (PDI) and then after a dose adjustment period using slow-release L-dopa/benserazide (Madopar HBS) in an open inpatient trial. Three patients benefited from the slow-release preparation; two patients deteriorated with a tendency to have an unpredictable response, a delay to turn "on" with the first dose in the morning, as well as an increase in dyskinesia corresponding to L-dopa cumulation during the day. These problems were subsequently also seen during the follow-up period of 1 year in those patients who benefited from Madopar HBS as inpatients. This might indicate that patient compliance is more difficult with the new formulation. After 1 year all patients had returned to their previous standard L-dopa/PDI treatment. L-Dopa levels continued to fluctuate, but to a lesser degree with Madopar HBS. The equivalent L-dopa dosage had to be increased by 56% (29-100%) with Madopar HBS while mean dopamine levels increased in four patients (by 47-257%) without the occurrence of peripheral side-effects. This implies that with the new formulation more L-dopa is metabolized to dopamine and explains the necessity to increase the equivalent L-dopa dosage.
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PMID:Controlled-release levodopa/benserazide (Madopar HBS): clinical observations and levodopa and dopamine plasma concentrations in fluctuating parkinsonian patients. 218 Oct 74

In this multicentre study a controlled-release formulation of levodopa and the decarboxylase inhibitor benserazide (Madopar CR) was evaluated in patients with Parkinson's disease exhibiting dose-related fluctuations in motor performance in response to conventional levodopa preparations. The effect of Madopar CR, with or without conventional levodopa/benserazide, on the proportion of time spent "on", "off" or "intermediate" was compared with that of previous conventional levodopa/decarboxylase inhibitor therapy. Evaluation of the two periods of optimum therapy was based on both patient diary data and investigator opinion. Forty seven patients completed the study but full patient diaries were available for only 37. The mean optimum total daily dosage of conventional Madopar was 820 mg taken in a mean of 6.4 doses, compared with a mean optimum daily dosage of combined Madopar CR and conventional Madopar of 1088 mg, taken in a mean of 5.2 doses. Conventional Madopar was taken in addition to Madopar CR in all but eight patients. Madopar CR was felt to be advantageous in 83% and disadvantageous in 11% of patients completing the study. Considering the 37 patients for whom diary data were available, Madopar CR therapy resulted in an increase in the mean time spent "on" (p = 0.016) and a decrease in the mean time spent "off" (p = 0.029) compared with conventional Madopar alone. Individually 25 out of 37 had an increase in "on" time and 19 out of 37 experienced a decrease in "off" time. Thus Madopar CR was found to be beneficial in a significant proportion of patients experiencing fluctuations in response to conventional levodopa.
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PMID:A comparison of the effects of controlled-release levodopa (Madopar CR) with conventional levodopa in late Parkinson's disease. 218 81

Madopar Hydrodynamically Balanced System (HBS), a new sustained-release levodopa preparation, was used to control severe nightly disabilities in 15 outpatients suffering from Parkinson's disease in an advanced state and with long-term levodopa therapy. This medication was given ante noctem in addition to an otherwise unchanged daily regimen of levodopa administration. In 13 patients a considerable diminution in nocturnal akinesia and in the frequency of waking up was reached with a mean dosage of 308 mg of Madopar HBS. Early morning akinesia was only slightly alleviated in four patients. The nocturnal off-period pain disappeared in one patient. Adverse effects consisted of nocturnal dyskinesia in two patients and early morning dystonia in another two patients. The regular use of sleeping pills was clearly reduced after Madopar HBS therapy.
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PMID:Madopar HBS in nocturnal symptoms of Parkinson's disease. 223 93

The efficacy of a novel oral sustained-release preparation of levodopa/benserazide (Madopar HBS) was compared to that of previous conventional levodopa/benserazide treatment in 15 patients with idiopathic Parkinson's disease and with severe fluctuations in motor response to long-term levodopa therapy. In ten patients who suffered from clear-cut "end-of-dose" deterioration, significant benefit was obtained on HBS form, while 5 patients did not respond well to the new levodopa preparation. Plasma levels of levodopa were more stable with HBS compared to conventional levodopa preparation in our patients, although doses of HBS form required for an optimal response averaged 1.48 times that of previous conventional levodopa.
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PMID:Open study of sustained-release formulation of levodopa and benserazide in parkinsonian patients. 226 52

Therapeutic responses to Sinemet CR were studied in 37 patients with early Parkinson's disease previously treated with standard (Madopar) or controlled-release (Madopar HBS) levodopa/benserazide combinations. Patients were followed up for a 3-month period. The optimal therapeutic response of parkinsonian disability to Sinemet CR was equal to that obtained with Madopar or Madopar HBS. The optimal therapeutic dosage of Sinemet CR was equal to that of Madopar HBS but 12% higher than that of standard Madopar. However, with Sinemet CR treatment, the number of daily doses needed was significantly fewer than with both previous treatments. End-of-dose failure, which had developed in 4 patients, and peak-dose dyskinesias present in 6 patients during treatment with standard Madopar, improved significantly with Sinemet CR. Thus, Sinemet CR seems to be beneficial and useful in the treatment of early Parkinson's disease.
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PMID:Treatment of early Parkinson's disease with controlled-release levodopa preparations. 258 66

In a double-blind, crossover study, 103 patients with Parkinson's disease and nocturnal and/or early-morning disabilities took a bedtime dose of either Madopar CR (controlled-release levodopa plus benserazide) or standard Madopar, in addition to their usual daytime levodopa regimen. The mean optimum dosages were as follows: Madopar CR, 2.4 125 mg capsules; standard Madopar, 2.2 125 mg capsules. Assessment by daily patient diary and the doctor's record showed that nocturnal and early-morning disability was reduced by both treatments compared with at the start of the study, the difference being statistically significant. Improvement occurred in a similar number of patients when taking Madopar CR or standard Madopar (nocturnal disability improved in 61% on Madopar CR, and 57% on standard Madopar: early-morning disability improved in 46% on Madopar CR, and 44% on standard Madopar) and the percentage of patients wishing to continue on each treatment was also similar (64% on Madopar CR, and 55% on standard Madopar). However, in two-thirds of all cases, both doctor and patient felt that there was a difference between the treatments. Both Madopar CR and standard Madopar were of benefit to patients with nocturnal disability and, to a lesser extent, to those with early-morning problems. However, some patients responded better to Madopar CR and some to standard Madopar.
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PMID:A comparison of Madopar CR and standard Madopar in the treatment of nocturnal and early-morning disability in Parkinson's disease. The U.K. Madopar CR Study Group. 269 Oct 69


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