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)

Apomorphine, a potent dopamine agonist with mixed D1 and D2 properties, has long been recognized to have antiparkinsonian effect. Its oral administration is limited by both its hepatic first pass metabolism and adverse side effects (nausea, vomiting, azotemia). It is now widely used by subcutaneous route for the treatment of severe "off" periods seen with levodopa treatment. However, the use of penjects can be difficult in some patients with severe tremor or akineto-rigid symptoms during "off" periods. Our group has recently investigated the effect of sublingual administration of apomorphine in patients suffering from Parkinson's disease. Sublingual apomorphine was shown to reduce extrapyramidal symptoms. The main characteristics of the pharmacodynamic effects of sublingual apomorphine in parkinsonians and the relationship between pharmacodynamic and pharmacokinetic effects are discussed. Sublingual apomorphine has the advantage of being easier to administer than subcutaneous injection. For the moment, the long-term use of sublingual apomorphine is limited by two major problems: first, time for dissolution and switch "on" (which is longer than after subcutaneous route) and secondly, the occurrence of local side effects (stomatitis). Further clinical studies using either more efficient (tablets with faster dissolution) and better tolerated sublingual formulations or other dopamine agonists should be carried on before recommending this approach in the treatment of Parkinson's disease.
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PMID:Sublingual apomorphine: a new pharmacological approach in Parkinson's disease? 874 21

In the past 15 years, clinical data of over 1,500 patients treated with pergolide mesylate have been published. Pergolide is a dopamine agonist with a potent stimulating effect on D2 and also on D1 receptors. This pharmacodynamic characteristic seems the most effective in increasing the motility in Parkinson's disease. Pergolide has been used almost exclusively as an adjunct to levodopa treatment. Its positive effects seems to be related to its long plasma half life, about 27 hours, and 5-6 hours of clinical activity; it has shown to be effective on all parkinsonian symptoms except for the reduction of postural reflexes, it reduces off periods and compared to bromocriptine, it considerably improves the activities of daily living. Adverse reactions are, for the most part, mild and reversible, they mostly include nausea and gastroenteric disturbances.
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PMID:Pergolide mesylate in Parkinson's disease treatment. 874 27

We studied the nature and frequency of nonmotor "off" phenomena in 130 consecutive patients with Parkinson's disease (PD) with motor fluctuations. Twenty-two patients (17%) experienced nonmotor fluctuations as an end-of-dose phenomenon. Previously unreported, or little appreciated, nonmotor "off" states include sensory dyspnea, nausea, facial flushing, cough, hunger, unilateral limb edema, proximal limb pain, and trigeminal neuralgia-like pain. We attempted treatment modification in 12 of 22 patients; nonmotor "off" symptoms improved in nine of these 12 patients (75%). Recognizing these phenomena will prevent unnecessary tests and treatments.
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PMID:Nonmotor fluctuations in patients with Parkinson's disease. 937 51

A total of 335 patients with early Parkinson's disease (PD) were enrolled in a multicenter, randomized, double-blind trial designed to assess the efficacy and safety of pramipexole. Entry was restricted to patients with idiopathic PD who were not receiving levodopa. Pramipexole was administered according to an ascending dose schedule up to 4.5 mg/d. During the 7-week dose-escalation phase, each subject was titrated to his or her maximally tolerated dose of study medication. This was followed by a 24-week period of maintenance therapy. The mean daily dose during the maintenance period was 3.8 mg. Pramipexole significantly reduced the severity of PD symptoms and signs compared with placebo, as measured by decreases in parts II (Activities of Daily Living) and III (Motor Examination) of the Unified Parkinson's Disease Rating Scale at week 24 compared with baseline (p < or = 0.0001). Differences between the active drug and placebo groups emerged at week 3 (1.5 mg/d) in the ascending-dose interval and persisted throughout the maintenance phase (p < or = 0.0001). The majority of patients completed the study (pramipexole 83%, placebo 80%). In the assessment of adverse events, nausea, insomnia, constipation, somnolence, and visual hallucinations occurred more frequently in the pramipexole treatment group compared with placebo patients. No clinically significant changes were noted in blood pressure or pulse rate. Overall, these results indicate that pramipexole is safe and effective in the treatment of early PD.
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PMID:Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson's disease. The Pramipexole Study Group. 930 31

Pramipexole is a new, selective, nonergoline dopamine agonist that acts on D2 and preferentially on D3 dopamine receptors. Phase II and III clinical trials have shown this drug to be useful in treating both early and advanced Parkinson's disease (PD) patients. A double-blind, randomized, multicenter study was performed to compare the safety, tolerance, and efficacy of pramipexole versus placebo in patients with advanced PD with motor fluctuations. A bromocriptine treatment group was included to enable comparisons between bromocriptine and placebo groups, but the study was not powered to show statistical differences between the active treatment groups. The study included 247 patients with "wearing off." Patients were Hoehn and Yahr stages II to IV during "on" times. The trial included three phases: dose escalation, 6 months' maintenance, and dose reduction. The primary end points were the Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III. Up to 4.5 mg per day of pramipexole and 30 mg per day of bromocriptine were used. The results of the study showed that the UPDRS part II improved by 26.7% for pramipexole (p = 0.0002) and 14% for bromocriptine (p = 0.02) versus 4.8% for placebo. The UPDRS part III showed improvements of 34% for pramipexole (p = 0.0006) and 23.8% for bromocriptine (p = 0.01) versus 5.7% for placebo. There were no major differences in safety data. In the active treatment groups there were more reports of dyskinesia and nausea compared with placebo. In regard to comparison of the Global Clinical Assessment of Efficacy between active treatment groups, there was a trend to significance (p = 0.056) in favor of pramipexole. We conclude that pramipexole-treated patients with advanced PD improved significantly more than placebo for both primary end points.
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PMID:Double-blind comparison of pramipexole and bromocriptine treatment with placebo in advanced Parkinson's disease. International Pramipexole-Bromocriptine Study Group. 933 90

The primary objective of this study was to assess the effect of tolcapone on levodopa dosage in parkinsonian patients whose "wearing-off" phenomenon has been controlled with more frequent levodopa dosage. After a 1-week placebo run-in, 97 patients were assigned randomly to receive placebo or tolcapone 200 or 400 mg three times daily (t.i.d.). Levodopa dosage was reduced by -35% on day 1 of study and subsequently retitrated as required. After 6 weeks, the tolcapone groups crossed over to receive the other dose for a further 3 weeks for exploratory purposes. Both tolcapone groups had greater reductions in levodopa dosage than the placebo group at week 6 (not statistically different). The 200-mg t.i.d. group showed greatest improvement in estimated mean scores for all efficacy parameters (p < 0.05 versus placebo for change in Unified Parkinson's Disease Rating Scale Subscale II). Fewer dopaminergic and nondopaminergic adverse events were associated with tolcapone 200 mg t.i.d. than with tolcapone 400 mg t.i.d. The most frequently reported dopaminergic adverse events were nausea, cramps, dyskinesia, and dystonia. The most frequently reported unanticipated adverse event was diarrhea. Tolcapone 200 mg t.i.d. may provide additional benefit to patients with moderately advanced Parkinson's disease with treated "wearing-off" phenomenon.
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PMID:Tolcapone added to levodopa in stable parkinsonian patients: a double-blind placebo-controlled study. Tolcapone in Parkinson's Disease Study Group II (TIPS II). 939 17

This study investigated whether domperidone could improve gastrointestinal symptoms in patients with Parkinson's disease who were receiving levodopa therapy. A total of 11 patients were studied. Following a baseline gastric emptying test, patients were treated with a starting dose of domperidone 20 mg p.o. q.i.d. A follow-up gastric emptying test was repeated at least 4 months after starting domperidone therapy. At the beginning and at each 3-month follow-up visit, symptoms of nausea, vomiting, anorexia, abdominal bloating, heartburn, regurgitation, dysphagia, and constipation were evaluated and scored on a scale of 0-3. The overall mean follow-up period was 3 years. Compared with their baseline evaluation, patients experienced a significant improvement in all symptoms (p < 0.05) except dysphagia and constipation. Gastric emptying of an isotope-labeled solid meal was significantly faster, with a baseline result of 60.2 +/- 6.4% retention of isotope 2 h after the meal compared with 37.0 +/- 2.2% retention during domperidone therapy (p < 0.05). Patients' global assessment of Parkinson's disease remained stable or improved. Serum prolactin was elevated in all patients after domperidone therapy (p < 0.05). Domperidone therapy significantly reduces upper gastrointestinal symptoms and accelerates gastric emptying of a solid meal, but does not interfere with response to antiparkinsonism treatment.
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PMID:Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with Parkinson's disease. 939 20

The efficacies of ropinirole and levodopa were compared after 6 months of treatment in a planned interim analysis of a 5-year, double-blind, randomized, multicenter study of patients with early Parkinson's disease requiring dopaminergic therapy. The percentage of improvement in the Unified Parkinson's Disease Rating Scale total motor examination score was significantly higher for levodopa (44%) than for ropinirole (32%). The proportion of "responders" (Unified Parkinson's Disease Rating Scale improvement of at least 30%) did not differ between groups (levodopa, 58%; ropinirole, 48%). There was no difference between the groups for improvement on the Clinical Global Impression scale in patients with Hoehn and Yahr stages I, I.5, or II, but a significantly higher proportion of patients with Hoehn and Yahr stages II.5 or III showed Clinical Global Impression score improvement with levodopa. Emergent adverse events occurred in 84% of patients in both treatment groups, the principal symptom in each group being nausea. The incidence of serious adverse events was low (8% for ropinirole, 9% for levodopa). The results suggest that ropinirole and levodopa are equally effective in less severe Parkinson's disease; in more advanced Parkinson's disease, levodopa is superior.
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PMID:Ropinirole in the treatment of early Parkinson's disease: a 6-month interim report of a 5-year levodopa-controlled study. 056 Study Group. 945 24

We compared the efficacy and safety of ropinirole with that of bromocriptine after 6 months of treatment in a planned interim analysis of a 3-year, double-blind, randomized, multicenter study of 335 patients with early Parkinson's disease requiring dopaminergic therapy. Patients, treated with or without selegiline, received either ropinirole or bromocriptine. The mean Unified Parkinson's Disease Rating Scale (UPDRS) total motor examination scores (Part III) at baseline were similar in the four strata. Overall, and in the non-selegiline subgroup, the percentage improvement in the UPDRS total motor examination score was significantly higher for ropinirole than for bromocriptine, as was the proportion of "responders." In the selegiline subgroup, however, there was no significant difference between treatments. Similarly, in the non-selegiline subgroup, there was a significantly higher proportion of "improvers" on the Clinical Global Impression scale with ropinirole than with bromocriptine, whereas in the selegiline subgroup, there was no significant difference. Emergent adverse events occurred in 80% of patients in both treatment groups, the principal symptom in each group being nausea. The incidence of serious adverse events was low (3% for ropinirole, 6.6% for bromocriptine). The data indicate that (a) in the absence of selegiline, ropinirole is effective and superior to bromocriptine; and (b) selegiline does not affect the response in patients treated with ropinirole, but enhances the effects of bromocriptine.
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PMID:Ropinirole versus bromocriptine in the treatment of early Parkinson's disease: a 6-month interim report of a 3-year study. 053 Study Group. 945 25

The efficacy and safety of ropinirole, a novel nonergot dopamine D2-like receptor agonist, was assessed as monotherapy for the treatment of patients with early-stage Parkinson's disease. In this double-blind, multicenter trial, patients were randomly allocated in a ratio of 2:1 to receive, over a 12-week period, either ropinirole or placebo. Clinical status was assessed using the Unified Parkinson's Disease Rating Scale (UP-DRS), Clinician's Global Evaluation (CGE), and a finger-tapping score. In all, 41 patients received ropinirole and 22 received placebo. The end-point analysis, on an intention-to-treat basis, revealed a significant difference (p = 0.018) in improvement in UP-DRS motor score from baseline between treatment groups (ropinirole, 43.4%; and placebo, 21.0%). Other parameters, including the number of responders and improvement in CGE, showed similar results. Three patients in the ropinirole group and one patient in the placebo group discontinued the study because of adverse events. There was no significant difference between the treatment groups in the overall incidence of adverse events. Although the dopaminergic side effects were reported significantly more frequently in the ropinirole group than in the placebo group (dizziness, p = 0.0326; nausea, p = 0.001; and somnolence, p = 0.005), none necessitated study withdrawal. There was no evidence of any chronic effect of the study medication on vital signs. In conclusion, ropinirole is a safe and well-tolerated drug and, as monotherapy, provided significant therapeutic benefit compared with placebo to patients in the early stages of Parkinson's disease.
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PMID:A placebo-controlled evaluation of ropinirole, a novel D2 agonist, as sole dopaminergic therapy in Parkinson's disease. 957 96


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