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)

Almost all patients with idiopathic Parkinson's disease respond to levodopa and progress steadily, requiring an increased overall dosage with time. Sinemet CR4 offers a theoretically attractive method of achieving gradual sustained release of levodopa over time which may be more physiological to striatal dopamine receptors in the early stages of the disease. This study evaluated 20 patients with moderate to severe Parkinson's disease who were treated with Sinemet CR4 over a 1-year period. Eleven patients completed the full year on therapy, and nine subjects withdrew. Of the withdrawals, two subjects died from non-Parkinson's disease-related illness, three showed no therapeutic benefit, and four responded well for a minimal 6-month period, but then lost therapeutic benefit and developed more severe dystonias. A higher overall levodopa dosage was required by all patients, and side-effects of levodopa were still present in most patients. However, the nocturnal benefit of this long-acting preparation was observed by all the patients in the study. Slow onset of action of Sinemet CR4 resulted in early-morning immobility. Sinemet CR4 cannot replace standard Sinemet, but appears to be a useful form of adjunct therapy in selected patients.
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PMID:Sinemet (CR4): an open-label study in moderately severe Parkinson's disease. 186 61

Thirty-eight patients newly diagnosed as having Parkinson's disease (mean age, 57.3 years; mean Parkinson's disease duration, 2.7 years) in the earlier phase of the disease (mean Hoehn/Yahr stage, 2; mean motor scores, 11.4) were given selegiline (Deprenyl), 10 mg daily, and maintained on this drug alone until significant clinical worsening warranted the addition of low-dose levodopa (Sinemet, 25/100 three to four doses per day). Five of these patients were not yet receiving additional levodopa despite some worsening of motor scores. Of the 33 patients now taking combined therapy, seven have been followed up for 6 months or less. Twenty-four (92%) of the 26 patients taking combined therapy for a mean of 26 months (8.5 to 99 months) who have had Parkinson's disease for 6 years showed a dramatic improvement in their parkinsonism shortly after the addition of levodopa, with significant decreases in their rated motor scores, such improvement being maintained at their latest neurologic evaluation. Eighteen (75%) of these 24 patients responded to the combined selegiline/levodopa therapy with degrees of improvement equal to or greater than 50%, compared with their motor status at the start of combined therapy just before the addition of levodopa. This degree of "reversal" of parkinsonism on addition of levodopa (mean carbidopa/levodopa dose, 98/389 mg) was not observed in any of these same patients receiving selegiline alone for an average of 13.8 months. Four patients taking combined therapy developed mild, transient, abnormal involuntary movements, and end-of-dose pattern of response after more than 2 years of combined therapy (24.75 and 33.5 months, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early combination of selegiline and low-dose levodopa as initial symptomatic therapy in Parkinson's disease. Experience in 26 patients receiving combined therapy for 26 months. 192 87

Parkinson's disease affects thousands of Americans, men and women equally and apparently with little regard to race. Its diagnosis depends largely on repeated clinical observations of representative signs, such as resting tremor, rigidity, bradykinesia, and gait disturbances. Patients progress through stages: Early disease involves only one limb or side and confers minimal disability, but advanced disease restricts patients to full care. Treatment is chosen on the basis of disease stage and patient response. Combination carbidopa-levodopa (Sinemet) is appropriate for any significant degree of disability, and other antiparkinsonian drugs and anticholinergic agents may be used as adjuncts. Electroconvulsive therapy, use of selegiline hydrochloride (Eldepryl), and surgery are still undergoing investigation but may hold promise.
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PMID:Treating the progressive stages of Parkinson's disease. 190 7

Twenty patients with moderately severe Parkinson's disease entered an open study of the efficacy and safety of a slow release preparation containing levodopa 200 mg and carbidopa 50 mg per tablet ('Sinemet CR4'). Following an initial four week baseline stabilisation period on conventional 'Sinemet' tablets, the patients were transferred to 'Sinemet CR4' and observed at intervals over the next 12 months. Fifteen patients completed the full year observation period. When compared with the baseline period, treatment with 'Sinemet CR4' was associated with longer periods of functional improvement and less fluctuation of response following each dose. The median (range) dose frequency was reduced from three (three-12) to two (two-seven) times daily (p less than 0.001) on 'Sinemet CR4' although median (range) total daily dose of levodopa was increased from 700 (375-2525) to 800 (400-2800) mg without any increase in adverse effects. Three patients developed peripheral neuropathy while receiving Sinemet CR4, but the association with this therapy is unclear. Overall 'Sinemet CR4' allowed a longer dosage interval and provided more stable control of disease manifestations than conventional 'Sinemet'.
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PMID:Controlled release levodopa/carbidopa (Sinemet CR4) in Parkinson's disease--an open evaluation of efficacy and safety. 195 26

Ten patients with Parkinson's disease (PD) with motor fluctuations that responded to a protein redistribution diet were studied. All 10 patients were receiving standard Sinemet (levodopa/carbidopa). Five randomly selected patients were changed from standard Sinemet to a controlled-release form of Sinemet. The other five patients continued to receive standard Sinemet. To maintain the same degree of control of PD in the five patients switched to the controlled-release form of Sinemet, the daily levodopa intake increased. While receiving optimal therapy (standard Sinemet or controlled-release Sinemet) and a protein redistribution diet, all 10 patients then underwent hourly videotaping and blood sampling (for plasma levodopa levels) during 2 consecutive days. Videotapes were blindly reviewed for PD disability, dyskinesia, and the time required to walk a measured distance. Comparing the two groups, standard Sinemet with controlled-release Sinemet, respectively, mean levodopa requirements were 505 and 1895 mg, plasma levodopa levels were 6.1 and 17.6 mumol/L, and abnormal involuntary movement scale scores were 14 and 26. Their mean PD disability scores did not differ statistically or clinically. Also no statistically significant differences were noted in either their mean walking times or their mean daily dose frequencies.
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PMID:Standard and controlled-release levodopa/carbidopa in patients with fluctuating Parkinson's disease on a protein redistribution diet. A preliminary report. 201 14

It has been proposed that initiation of anti-Parkinson therapy with continuous release formulations of Sinemet might prevent or delay the development of adverse effects associated with chronic levodopa therapy employed in standard formulations. In anticipation of a prospective study comparing Sinemet to Sinemet CR in previously untreated Parkinson's disease patients, we evaluated Sinemet CR as primary therapy in 45 levodopa-naive Parkinson's disease patients in a 12 week, open-label, multi-center study. At the conclusion of the study, optimal results were obtained with levodopa administered as Sinemet CR in a total daily dose of 497 mg divided into 2.4 doses per day. Statistically significant improvement compared to baseline was observed for total Parkinson's score as well as each of rigidity, tremor, bradykinesia, gait and postural stability. Statistically significant improvement was also noted in total disability as well as in each of its components. Adverse experiences were mild and transient and no significant laboratory abnormalities were encountered. We conclude that a daily dose of 1 to 1.5 tablets b.i.d. of Sinemet CR as primary therapy for patients with Parkinson's disease is well tolerated and provides effective therapy.
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PMID:An open multicenter trial of Sinemet CR in levodopa-naive Parkinson's disease patients. 207 Mar 63

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

Six patients with Parkinson's disease (PD) and therapeutic response fluctuations (RF) on levodopa treatment participated in an open-label trial of L-deprenyl (Eldepryl) in conjunction with Sinemet. Deprenyl (10 mg/day) allowed a slight but not statistically significant 22% reduction of total daily levodopa intake after 4 weeks of treatment, with a significant but unsustained reduction in the number of daily "off" periods and an increase in the portion of waking day spent "on." Pharmacokinetic studies revealed no effect of deprenyl on the plasma levodopa concentration vs. time curve, or the coefficient of variation (C.V.) of plasma levodopa levels measured over an 8-h period. Plasma DOPAC levels were unaffected, suggesting that the majority of peripheral DOPAC is generated by action of MAO-A. For most patients, benefit was not maintained. Two patients have continued taking the drug, and both have enjoyed significant reductions in total levodopa dose. Both have mild end-of-dose failure and little dyskinesia. Since no changes in peripheral pharmacokinetics of levodopa could be demonstrated, any therapeutic action of deprenyl in PD would appear to be due to prolongation of dopaminergic activity within the CNS.
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PMID:L-deprenyl, levodopa pharmacokinetics, and response fluctuations in Parkinson's disease. 210 91

35 Parkinson's disease patients with motor response fluctuations (RF) participated in controlled clinical trials comparing Sinemet CR to Standard Sinemet (STD) at our institutions. 13 of 25 eligible patients continued to two years (the longest possible follow-up from the second study), and 5 of 11 have continued taking CR up to 4 years. At the end of both two and four years, patients were taking significantly fewer medication doses, with a significantly longer interdose interval, and up to two years, experienced fewer "off" periods than when on Standard Sinemet (STD) alone. Most patients required STD at at least one dose each day to hasten to onset of antiparkinson effect. Sinemet CR is a useful adjunct in the long-term management of motor response fluctuations in Parkinson's disease.
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PMID:Results of long-term treatment with controlled-release levodopa/carbidopa (Sinemet CR). 225 60

1. This study examined the effects of administering ferrous sulphate 325 mg with Sinemet (100/25 tablet) on levodopa and carbidopa bioavailability and on signs of Parkinson's disease in nine patients. 2. Ferrous sulphate ingestion with Sinemet resulted in a decrease in levodopa area under the curve (AUC) of 30% (P less than 0.01) and a greater than 75% decrease in carbidopa AUC. Despite a strong relationship between reductions in levodopa AUC and reductions in Sinemet efficacy (r = 0.83, P less than 0.01), the average reduction in Sinemet's efficacy associated with ferrous sulphate did not achieve statistical significance (P = 0.055). 3. Chemical studies indicate that iron forms chemical complexes with carbidopa in a similar manner to levodopa and is a likely mechanism for the drug interactions. 4. AUC when a Sinemet tablet is taken concurrently with a ferrous sulphate tablet appears to be clinically significant in some but not all patients. The clinical significance of repeated ingestion of ferrous sulphate with Sinemet requires further studies.
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PMID:Sinemet-ferrous sulphate interaction in patients with Parkinson's disease. 229 72


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