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)

Eight Parkinson patients with response fluctuations completed an open-label trial of a controlled-release carbidopa/levodopa preparation (Sinemet CR3). At the end of 6 weeks, percent "on" time and mean interdose interval increased, the number of daily doses and "off" periods was decreased, and the variability of plasma levodopa levels and disability scores was reduced. However, response fluctuations continued to occur, day-to-day consistency was poor, and the bioavailability of levodopa appeared less than that of standard Sinemet. Overall benefit waned over the next 3 to 6 months. Oral controlled-release carbidopa/levodopa is capable of reducing fluctuations in plasma levodopa levels and clinical performance in Parkinson's disease. The response to this particular controlled-release formulation was suboptimal and unsustained.
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PMID:Controlled-release levodopa/carbidopa. I. Sinemet CR3 treatment of response fluctuations in Parkinson's disease. 380 4

Pergolide mesylate, a dopamine agonist, was studied as adjunctive therapy in a 6-month double-blind trial in 20 patients with Parkinson's disease who were achieving less than optimal response from Sinemet. As pergolide or placebo was administered in increasing dosage, Sinemet was reduced if side effects developed. Both the pergolide and placebo groups improved significantly (p less than 0.05). The pergolide group improved 30% at the end of 24 weeks, and the placebo group 23%. There was no significant difference between drug and placebo groups, possibly due to a fortuitous support group and the side effects that may have burdened the pergolide group. Nevertheless, pergolide had a definite antiparkinsonian effect.
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PMID:Double-blind trial of pergolide for Parkinson's disease. 388 32

The efficacy of low-dose bromocriptine mesylate administration (20 mg daily or less) was evaluated in a double-blind study. Nine of 16 individuals receiving bromocriptine completed the 40-week study. Modest, but significant, improvement was derived from bromocriptine therapy. Improvement was most evident in tremor. Maximum improvement was achieved with doses between 7.5 and 15.0 mg daily, with some decline in efficacy as doses approached 20 mg. Adverse effects were common, but were generally mild in severity. Our results suggest that bromocriptine in low doses may be an effective adjunct to carbidopa and levodopa (Sinemet) in the treatment of Parkinson's disease.
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PMID:Low-dose bromocriptine therapy in Parkinson's disease. 400 3

In a general practice population of 57 000, 32 patients suffering from Parkinson's disease were identified from repeat prescription indexes and direct questioning of all members of the primary health care team. Of these patients 26 were receiving an L-dopa preparation and 10 an anticholinergic drug. The only newer drug found to be in use was bromocriptine and three patients were receiving this treatment.Of the 26 patients receiving an L-dopa preparation one received L-dopa alone, six L-dopa with benserazide (Madopar, Roche) and 19 L-dopa with carbidopa (Sinemet, Merck, Sharp and Dohme). The patients treated with Sinemet were receiving inadequate doses of carbidopa - three quarters received less than 75 mg per day which was in part a reflection of the low doses of L-dopa the patients received, the average dose being 468 mg per day. The L-dopa preparations were given in adequately spaced doses.The general practitioner made the diagnosis in 20 of the 32 cases and was in control of the drug therapy in 15 cases, however 25 cases were referred for specialist advice.
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PMID:Audit of the drug treatment of Parkinson's disease in general practice. 403 54

We evaluated pergolide in 22 patients with Parkinson's disease and 3 with progressive supranuclear palsy (PSP). After achieving an optimal dose of pergolide and Sinemet, a matching placebo was substituted in double-blind manner. The mean dose of levodopa (in Sinemet) was reduced by 68%; in eight patients, pergolide completely replaced levodopa. In parkinsonian patients, the mean Hoehn-Yahr stage decreased from 3.2 to 1.6, and the mean total disability score decreased from 48.3 to 17.8. In 10 patients with on-off phenomenon, the time on increased 174% with pergolide. There was little effect in PSP. Postural light-headedness and reversible mental changes were seen.
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PMID:Controlled trial of pergolide mesylate in Parkinson's disease and progressive supranuclear palsy. 633 85

Twenty-eight patients with Parkinson disease (PD) were treated with bromocriptine for at least 2 years (mean, 2.8 years; range, 2 to 5 years). All of them had first been treated with levodopa (alone or combined with carbidopa, as Sinemet) for 7.4 years (range, 1 to 10 years). At the time bromocriptine was started, all were showing increasing disability. In these patients, attempts to increase levodopa resulted in adverse effects, and attempts to decrease levodopa resulted in increased parkinsonism. Bromocriptine (mean daily dose, 56 mg) was added to levodopa and resulted in improvement of at least one stage (Hoehn and Yahr scale) in 21 of the patients. After 2 years, five of these patients continue to maintain this improvement. The remaining patients, although there has been deterioration, maintain some of their original improvement. Bromocriptine, when added to levodopa, results in improvement that is maintained, in part, for at least 2 years. The ratio of bromocriptine to levodopa has to be periodically readjusted.
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PMID:Long-term efficacy of bromocriptine in Parkinson disease. 676 3

The thyrotrophin (TSH) and prolactin (Prl)-releasing effects of TSH-releasing hormone (TRH) were investigated in 20 subjects with Parkinson's disease (PD), unmedicated, on chronic treatment with a combination levodopa-benserazide (Madopar) or levodopa-carbidopa (Sinemet) or withdrawn from therapy. Administration of TRH (200 micrograms iv) induced in unmedicated patients TSH and Prl responses significantly lower than those of sex-and age-matched controls. In patients on Madopar therapy the TSH and Prl responses to TRH were greater than in unmedicated patients and comparable to those of controls, while in patients on Sinemet therapy the pituitary responses were undistinguishable from those of unmedicated subjects. Withdrawal of Madopar therapy resulted in a marked diminution of the TSH response but did not affect the Prl response to TRH. Withdrawal of Sinemet therapy did not alter the TSH and Prl responses to TRH. Concomitant evaluation of growth hormone (GH) levels, in none of the subjects evidenced non-specific changes in plasma GH following TRH. Since TSH and Prl responses to TRH are inhibited by an enhancement of the dopaminergic tone, it would appear that the latter is preserved in the tuberoinfundibular system of unmedicated subjects and subjects on chronic Sinemet therapy, but is defective in subjects on chronic Madopar therapy.
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PMID:Thyrotrophin and prolactin responses to thyrotrophin-releasing hormone in patients with Parkinson's disease. 680 85

We studied the dopaminergic control of lactotroph cells in the anterior pituitary of parkinsonian patients and age-matched normal subjects. The resting levels of prolactin and the TRH-induced rise in prolactin were normal in Parkinson disease. Levodopa elicited a normal suppression of prolactin concentrations in parkinsonian subjects; the major abnormality to emerge was attenuation of the response to thyrotropin-releasing hormone (TRH) in the parkinsonian patients following administration of Sinemet (levodopa plus carbidopa) or bromocriptine. These findings imply pathology of extrastriatal dopamine systems in Parkinson disease. Since the addition of carbidopa enhanced the suppression of prolactin induced by levodopa, exogenous levodopa probably acts predominantly through the formation of dopamine in the hypothalamus, but inside the blood-brain barrier, rather than as a direct effect of circulating dopamine on the anterior pituitary or areas of the hypothalamus outside the blood-brain barrier.
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PMID:Prolactin secretion in Parkinson disease. 681 Feb 4

Thirty-seven patients with advanced Parkinson's disease who initially tolerated, and responded to bromocriptine therapy were followed for 12 to 50 (mean 28) months. Using a method of gradual increase of bromocriptine, with concomitant levodopa reduction, the peak effect of the drug was apparent by three months, at which time the mean daily dose of bromocriptine was 23.9 mg and Sinemet (levodopa + carbidopa) had been reduced by 34 percent. Eight patients had sustained improvement without further drug changes for an average of 29 (range 14-50) months. After periods of improvement varying between 3 and 30 months, 29 patients had a fall-off from peak effect. Peak effect was regained in 21 of these 29 patients for an average of 16 additional months by initially increasing bromocriptine or Sinemet, or by eventually increasing both drugs. The main adverse effect was a confusional state which necessitated late withdrawal of bromocriptine in four patients. The best results were in younger patients with end-of-dose deterioration and levodopa induced dyskinesias. With cautious introduction, and intermittent dosage adjustment, bromocriptine can be of long-term benefit to patients with advance Parkinson's disease. The majority of patients have a gradual late fall-off in effect which can frequently be reversed with dosage adjustment.
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PMID:Bromocriptine in the long-term management of advanced Parkinson's disease. 686 Oct 13

Lisuride, a semisynthetic ergoline and potent central dopamine and serotonin agonist, was combined with levodopa in 20 patients with advanced Parkinson disease who were no longer responding satisfactorily to levodopa, including 14 patients with "on-off' phenomena. Every patient who completed the 8-week trial improved significantly (p greater than or equal to 0.01), with a decrease in all symptoms. The mean dose of lisuride was 2.4 mg per day. The dose of levodopa (mg of levodopa in Sinemet) was reduced from 1030 to 920 mg. Among the patients with "on-off' phenomena, there was a significant increase in the time in which they were 'on' (mobile) from 4.6 to 9.6 hours. In 5 of 10 patients who have been on lisuride for at least 1 year, there has been no decline in efficacy.
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PMID:Lisuride combined with levodopa in advanced Parkinson disease. 703 4


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