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 long-term effect of selegiline (L-deprenyl) in the treatment of Parkinson's disease has not been clearly delineated. We report on a group of patients whose treatment was initiated with selegiline (n = 43) and then subsequently included L-dopa-carbidopa (Sinemet) and in whom an extended period of observation was carried out; they are compared to a group of patients whose treatment consisted of L-dopa-carbidopa alone (n = 39). In each, serial observations of the parkinsonian state and the response to treatment on a yearly basis for a period of 5 years were performed. No significant difference in the Hoehn-Yahr stage or in the motor subscores of tremor, rigidity, bradykinesia, and gait-posture was found between the two groups, nor was there a significant difference in the incidence of fluctuating responses or dyskinesias. The group that received combination therapy required less L-dopa than did the group that received L-dopa-carbidopa alone during the first 3 years of treatment and a similar trend was evident in years 4 to 5. We conclude that minimal benefits accrued to the parkinsonian patients from long-term use of selegiline. No clinical evidence to support the claim of "neuroprotective" properties was found. Selegiline's major usefulness is to modify the fluctuating therapeutic response seen with L-dopa-carbidopa.
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PMID:Comparative study of selegiline plus L-dopa-carbidopa versus L-dopa-carbidopa alone in the treatment of Parkinson's disease. 781 64

Three hundred and seventy-six subjects with advanced Parkinson's disease participated in a prospective, double-blind placebo-controlled study of the dopamine agonist pergolide mesylate as an adjunct to Sinemet. At 6 months, patients randomized to pergolide had a statistically significant improvement in total Parkinson's score, scores of activities of daily living, motor function, number of "off" hours, Hoehn and Yahr stage, and numerous parameters of parkinsonian function including bradykinesia, rigidity, gait, and dexterity. This benefit was obtained with the addition of a mean dose of 2.94 mg of pergolide, which permitted a 24.7% reduction in dose of levodopa. Adverse reactions were, for the most part, mild, reversible, and not of major clinical significance. No significant cardiac or electrocardiographic abnormalities were detected. This study demonstrates that pergolide mesylate, as an adjunct to levodopa, is an effective antiparkinsonian agent that provides clinical improvement while permitting a reduction in levodopa dose.
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PMID:A multicenter double-blind placebo-controlled trial of pergolide as an adjunct to Sinemet in Parkinson's disease. 813 4

Parkinson's disease responds rather dramatically to levodopa therapy during the first several years of treatment. With advancing disease, however, symptom control becomes more erratic, and some symptoms may become refractory to treatment. The use of selegiline hydrochloride (Eldepryl) has been proposed to slow the progression of Parkinson's disease; however, current evidence suggests that it is only partially effective at best, and there is no definite proof of a neuroprotective effect. Nonetheless, it is a reasonable treatment choice. Carbidopa-levodopa (Sinemet) remains the foundation of symptomatic treatment of Parkinson's disease. Clinical fluctuations occurring with advancing disease may be at least partially controlled by appropriate adjustments in dosage. A direct-acting dopamine agonist, bromocriptine mesylate (Parlodel) or pergolide mesylate (Permax), can be very helpful as adjunctive therapy to smooth these clinical fluctuations. Excessive intracellular oxidative stress has been proposed as a cause of Parkinson's disease; however, a recent multicenter trial investigating the use of high doses of the antioxidant vitamin E showed it to be ineffective. Whether other forms of nonspecific antioxidant therapy will prove beneficial is open to speculation.
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PMID:Treatment of Parkinson's disease. From theory to practice. 815 48

Motor performance of five patients with advanced Parkinson's disease was investigated during their optimum oral therapy (conventional tablets and/or depot capsules) and during a continuous duodenal infusion of levodopa. Due to the low water solubility of the drug, conventional tablets of levodopa+carbidopa (Sinemet) were milled and dispersed in a 1.8% aqueous methylcellulose solution. The dispersion was delivered nasoduodenally by a portable pump. The effect of levodopa in the two dosing regimens was estimated optico-electronically every 15 min and was also evaluated from videorecordings every 30 min and plasma levels of levodopa was regularly measured. Each dosage regimen the was studied twice, at a 2-4 day interval. Duodenal infusion improved motor function in all five patients and the fluctuations were reduced when compared to the oral therapy. Variation in plasma levodopa concentrations was 3-10 fold during oral therapy, while during the infusion a stable concentration was obtained. The therapeutic concentration varied from 0.3-3 ml-1 between patients. The relative bioavailability of levodopa in the solid preparation compared to the dispersion was in all patients 100%. Our results encourage further development of a duodenal infusion system with a levodopa dispersion for clinical use in parkinsonian patients who show severe fluctuation.
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PMID:Intraduodenal infusion of a water-based levodopa dispersion for optimisation of the therapeutic effect in severe Parkinson's disease. 822 31

Dyskinesia is a common adverse effect complicating chronic dopaminergic therapy for Parkinson's disease. Movements are frequently choreic in nature and have been ascribed to overstimulation of "supersensitive" striatal postsynaptic dopamine receptors. Anticholinergic medications, despite some clinical efficacy in Parkinson's disease, have rarely been reported to cause dyskinesia. We report a patient with Parkinson's disease who developed orobuccal dyskinesia while being treated with trihexyphenidyl (Artane). Dyskinesia was observed following the introduction of trihexyphenidyl, resolved with its discontinuation, and reappeared with its reinstitution. Carbidopa-levodopa (Sinemet) alone did not cause dyskinesia but augmented dyskinesia associated with trihexyphenidyl.
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PMID:Orobuccal dyskinesia associated with trihexyphenidyl therapy in a patient with Parkinson's disease. 784 12

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disease that responds poorly to pharmacologic intervention despite its clinical, neurochemical, and pathologic similarity to Parkinson's disease. We reviewed our experience with drugs used in the treatment of patients with PSP who were followed in the Department of Neurology, University of Medicine and Dentistry of New Jersey--Robert Wood Johnson Medical School. Of 136 patients identified, adequate drug-response data were available for 87 (64%). Benefit and adverse effects of therapy were graded on a 4-point scale: 0, none; 1, minimal; 2, moderate; 3, marked. The three most frequently used drugs were amitriptyline (32% of patients benefited), imipramine (28% of patients benefited) and levodopa/carbidopa (Sinemet) (38% of patients benefited). Levodopa/carbidopa, amantadine, selegiline, and amitriptyline gave the best risk/benefit ratios. Monotherapy tended to show more benefit and fewer adverse effects than polypharmacy.
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PMID:Retrospective study of drug response in 87 patients with progressive supranuclear palsy. 837 14

Sinemet-CR is manufactured by "Merck, Sharp and Dohme" firm (USA). It is represented the tablet form of drug that consists of levodopa (200 mg) and carbidopa (50 mg) on polymeric basis. This basis is dissolved gradually in small intestine providing prolonged drug's action. 29 patients in the age of 38-77 years with different forms of Parkinson's disease (1-13 years of duration) were treated using the doses 500-1500 mg. The doses depended upon both disease stage and individual sensitivity. It was also taken into consideration if the patients were or were not treated with levodopa and carbidopa preparations previously (the dose was adjusted during 3-4 weeks). The treatment's duration was 3 months. The positive medical effect was revealed in 23 cases (80%) while more expressed and firm effect was obtained in 15 cases. The most manifested action was observed toward rigidity, hypokinesia and tremor as well as toward such functions as memory, attention and psychical activity. Preparation's negative action was registered in 6 observations. In conclusion the authors noted both the high effectiveness and safety of preparation and recommended it for wide application.
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PMID:[The use of the Sinemet-CR preparation in treating Parkinson's disease]. 858 72

Only by adequate controlled studies can we be certain of the value of the different therapeutic choices available for the treatment of patients with PD. What may look favorable on preliminary open-label trials may not be confirmed on more rigorous controlled, randomized trials. This appears to be the case when reviewing the evidence for using dopamine agonists in early PD. Patients and clinicians await the results of the large double-blind, multicenter trial that compared bromocriptine alone, L-DOPA alone, and the two drugs in combination. Similarly, we await the results of a large multicenter, controlled trial comparing standard Sinemet and Sinemet CR in de novo patients with Parkinson's disease. The DATATOP study provided proof that selegiline can delay the need for L-DOPA, but it also showed for the first time that this drug has symptomatic effects in early PD. DATATOP failed to find conclusively a protective effect from selegiline. The long-running controversy whether L-DOPA is the culprit or the bystander in producing motor response fluctuations and the more recent concern as to whether it can hasten the progression of PD by producing increasing oxidative stress need to be answered; a prospective, controlled clinical trial might be able to provide these answers.
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PMID:Controversies in the therapy of Parkinson's disease. 861 68

We compared the pharmacokinetic and motor responses of Sinemet and Atamet (generic carbidopa/levodopa) in patients with Parkinson's disease. Thirty Parkinson's disease patients (10 previously untreated, 10 with early disease, and 10 with motor fluctuations/dyskinesia) participated in a single-dose double-blind study. Following administration of an equivalent oral dose of Sinemet and Atamet on two separate days, we compared the peak plasma concentration, time to peak plasma concentration, area under the curve, total motor score, tapping score, and walking time. The mean time to peak plasma concentrations was 49 min with Sinemet and 47 min with Atamet, the mean peak plasma concentration was 1,273 ng/ml with Sinemet and 1,153 ng/ml with Atamet, and the mean area under the curve was 2,295 micrograms/ml/h with Sinemet and 2,330 micrograms/ml/h with Atamet. Similarly, there was no significant difference between total motor score, tapping score, or walking time. In this single-dose study, there were no significant differences in pharmacokinetic and motor responses between Sinemet and Atamet.
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PMID:Pharmacokinetic comparison of Sinemet and Atamet (generic carbidopa/levodopa): a single-dose study. 881 23

Recently, there has been a surge in the research regarding the pharmacologic and surgical treatment of Parkinson's disease. This article reviews the latest modes of medical and surgical therapy for Parkinson's disease. The latest drug therapy has consisted of levodopa, a combination of levodopa and carbidopa (Sinemet/Sinemet CR), and monoamine oxidase type B (MAO-B) inhibitors (selegiline hydrochloride). The surgical treatment modalities have been stereotaxic implantations of dopamine-producing tissues (such as adrenal medulla and fetal mesencephalon) into the caudate nucleus and ventral pallidotomy of patients with Parkinson's disease. The most recent work has been in the field of gene therapy. The implantation of cells genetically modified to express trophic factors and tyrosine hydroxylase for the synthesis of L-dopa from tyrosine has been proposed as a possible route for the treatment of Parkinson's disease. Although the etiology of the disease is still unknown, two recent theories are discussed.
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PMID:Current trends in the pharmacologic and surgical treatment of Parkinson's disease. 893 28


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