Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nineteen patients with mild-to-moderate Parkinson's disease completed a 1-year open label study of a controlled release preparation of carbidopa/L-DOPA (Sinemet CR). Twelve patients were thought to have improved compared with baseline, and only one was worse. The total daily dose of L-DOPA was not significantly changed, but dosing frequency was almost halved. Patients with complex drug schedules on standard Sinemet liked the drug most. "Wearing off" patients also benefitted from the change, whereas "on/off" patients did not do significantly better on Sinemet CR.
 ...
PMID:An open trial of controlled release carbidopa/L-dopa (sinemet CR) for the treatment of mild-to-moderate Parkinson's disease. 274 46

PHNO, a new D-2 agonist, was investigated in five patients with Parkinson's disease. In an acute, open, oral, dose-ranging study comparing benefit from single doses, 4 mg of PHNO was found to be equivalent to one tablet of Sinemet 25/250 mg. Adverse reactions were those anticipated for a dopaminomimetic agent. Because of its novel structure and apparent transcutaneous penetration, further studies on PHNO are desirable.
 ...
PMID:Antiparkinsonian activity of a single oral dose of PHNO. 290 20

Patients with moderate to advanced Parkinson's disease may have prominent levodopa-related motor fluctuations. In a double-blind crossover study, we compared the anti-Parkinson effects of standard Sinemet with a controlled-release formulation (Sinemet CR-4) in 23 patients with short-duration responses to standard Sinemet. With Sinemet CR-4, approximately half the patients who completed the study displayed a prolongation of their "on" response (optimal response to treatment), as assessed by monitoring individual drug-response cycles. A few patients experienced prolonged delays before the peak anti-Parkinson response developed to Sinemet CR-4. End-of-dose "wearing off" was favorably affected by Sinemet CR-4, but patients still had unpredictable "off" (parkinsonian) periods. Subjective ratings of Sinemet CR-4 varied, and 39% of patients who completed the study actually preferred standard Sinemet to the new formulation. We conclude that Sinemet CR-4 may benefit some patients with Parkinson's disease with a short-duration response to standard Sinemet; however, not all patients found it preferable to the standard formulation.
 ...
PMID:Controlled-release Sinemet (CR-4): a double-blind crossover study in patients with fluctuating Parkinson's disease. 304 35

Previous short-term studies have shown that the dopamine agonist pergolide improves control of Parkinson's disease when used in conjunction with carbidopa-levodopa (Sinemet). We assessed the long-term outcome (2 1/2- to 3-year follow-up) in patients with Parkinson's disease who participated in our previous pergolide double-blind trial and were subsequently switched to open-label pergolide therapy. Of 41 evaluable patients who began pergolide therapy, 10 (24%) experienced sustained substantial benefit that persisted to the end of this investigation. A total of 23 patients (56%) remained on pergolide therapy and, as a group, had considerable improvement over baseline at 2 1/2 to 3 years on the basis of several measurements of efficacy. A tendency toward deterioration could be reversed in many patients by larger or more frequent doses of carbidopa-levodopa; nevertheless, all but four patients were still taking the same dose or less of carbidopa-levodopa at the end of this study as at the onset. Patients with the best initial response to pergolide seemed most likely to experience long-term benefit. Confusion and hallucinations were the side effects most likely to necessitate discontinuation of pergolide. Symptoms suggestive of dose-related angina pectoris occurred in four patients in the open-label phase and two patients in the earlier double-blind phase (13% of patients who started pergolide therapy); these symptoms were easily controlled by dose reduction or discontinuation of pergolide, without sequelae. Dose-related leukopenia developed in one patient.
 ...
PMID:Pergolide: long-term use in Parkinson's disease. 305 Mar 1

The combinations of benserazide and levodopa (1:4, Madopar) and of carbidopa and levodopa (1:10 and 1:4, Sinemet) are currently the most effective treatment of Parkinson's disease. In the present comparative study some effects of the peripheral aromatic L-amino acid decarboxylase (AADC) inhibitors benserazide and carbidopa administered alone or in combination with levodopa by the oral route were investigated in two animal species (rat and mouse) and in healthy volunteers. Benserazide is about 10 times more potent than carbidopa as inhibitor of peripheral AADC both in animals and man. Even at relatively high doses (up to 60 mumol/kg p.o.) benserazide is shown in animals to inhibit the decarboxylation of levodopa only in the extracerebral tissues, thus permitting the formation of dopamine in the striatum and in the hypothalamus. As benserazide is the most potent peripheral AADC inhibitor presently available, is well tolerated and relatively nontoxic even when used chronically, it appears to be the peripheral AADC inhibitor of choice for the development of controlled-release formulations in which Dopa is combined with a peripheral AADC inhibitor. When administered to healthy subjects the pharmacokinetics of the new drug delivery system named Madopar HBS (hydrodynamically balanced system) was characterized by lower and delayed plasma peak concentrations but a longer-lasting concentration of Dopa than after Madopar standard. Therefore, this new controlled-release system may reduce the clinical fluctuations occurring in patients with 'wearing-off' and 'on-off' phenomena.
 ...
PMID:Inhibition of decarboxylase and levels of dopa and 3-O-methyldopa: a comparative study of benserazide versus carbidopa in rodents and of Madopar standard versus Madopar HBS in volunteers. 312 42

Deprenyl, a selective inhibitor of monoamine oxidase, type B, which is free of the "tyramine effect," may ameliorate symptom fluctuations in advanced Parkinson's disease (PD). We randomized 96 patients with marked symptom fluctuations at three centers to receive either deprenyl 5 mg b.i.d. or placebo in parallel fashion in addition to a previously optimized levodopa/carbidopa (Sinemet) regimen. Disability was recorded hourly at home by patients 3 days weekly during the 2-week baseline and the 6-week treatment period. Disability during the "on" state was assessed each week by examination. Mean hourly self-assessment of gait improved in 28 of 50 patients (56%) receiving deprenyl (mean degree of improvement 0.25 points on a 0-2 scale) and in 14 of 46 (30.4%) taking placebo (mean 0.15). Mean hourly overall symptom control improved in 29 (58%) taking deprenyl (mean 0.34) and in 12 (26.1%) taking placebo (mean 0.15) (p less than 0.01 for each parameter). No significant improvement occurred in the objective quality of the "on" state with deprenyl. Mean daily Sinemet dosage decreases were 17% in the deprenyl group and 7% in the placebo group. Adverse effects included nausea, light-headedness, dyskinesias, and hallucinations, all of which abated after the Sinemet dose was reduced. We conclude that deprenyl is of moderate benefit in a majority of patients with symptom fluctuations complicating PD and is generally well tolerated.
 ...
PMID:Deprenyl in the treatment of symptom fluctuations in advanced Parkinson's disease. 312 50

The pattern visual evoked potential (PVEP) and pattern electroretinogram (PERG) were studied in 5 cynomolgus monkeys before and during the development of a parkinsonian syndrome induced by MPTP. The stimuli were vertical bars of four spatial frequencies (0.5, 1.2, 2.5 and 3.5 cycles/degree (cpd) modulated at temporal rates of 1, 4, 6, and 8 Hz. Following MPTP administration, all monkeys developed parkinsonian signs accompanied by changes in the amplitude and latency of the PVEP and PERG. Sinemet L-dopat carbi olopa administration produced temporary recovery of both PVEP and PERG. Two of the monkeys were followed for a prolonged period: 30-40 days after MPTP, the parkinsonian signs showed partial recovery; the PVEP latency and amplitude to 2.5 and 3.5 cpd stimuli and the latency to 1.2 cpd showed improvement but remained abnormal. The latencies of PERGs were normal, but the amplitudes were significantly reduced when stimuli of 2.5 and 3.5 cpd were used. Both PVEP and PERG to 0.5 cpd stimuli returned to normal. No further modifications were seen in the recordings performed 6 months and 1 year later. This study demonstrates (1) that spatial frequency-dependent electrophysiological abnormalities occur in the MPTP-treated monkey, a result previously found in human Parkinson's disease, and (2) that dopamine has a specific function in neurotransmission in the visual system of primates.
 ...
PMID:Spatial frequency-dependent abnormalities of the pattern electroretinogram and visual evoked potentials in a parkinsonian monkey model. 325 50

The first phase of a longitudinal multicenter study comparing bromocriptine and L-dopa (as Sinemet) as de novo therapy for Parkinson's disease using a double-blind randomized design has recently been completed. Over a period of 5.5 months, bromocriptine and L-dopa were equipotent in reducing functional and neurological disability. These observations complement and extend earlier studies and suggest a role for bromocriptine as de novo therapy of Parkinson's disease.
 ...
PMID:A double-blind study of bromocriptine and L-dopa in de novo Parkinson's disease. Short-term results. 328 77

Sixteen patients with advanced Parkinson's disease (PD) and motor fluctuations were evaluated throughout 12 months of open label therapy on CR4-Sinemet. Reduced dosage frequency and significant motor improvement with reduced fluctuation occurred and were maintained with CR4-Sinemet compared with baseline on Sinemet. In a double-blind protocol using CR4-Sinemet in 20 stable PD patients, CR4-Sinemet was given twice daily and compared with Sinemet given four times daily. Patients remained stable without improvement or deterioration when the long-acting drug was substituted at 50% frequency. Plasma levodopa levels with CR4-Sinemet were smoother than with Sinemet. Although some patients receiving CR4-Sinemet found they functioned more slowly in the morning, the easier dosing schedule and improved amount of "on" time in fluctuators suggest that this formulation may become increasingly useful in managing PD.
 ...
PMID:Controlled-release carbidopa/levodopa (CR4-Sinemet) in Parkinson's disease patients with and without motor fluctuations. 329 Jul 6

We evaluated 32 patients with Parkinson's disease in a double-blind, parallel group, placebo-controlled study with ciladopa (a troponylpiperazine derivative). The dosages administered were 5 mg b.i.d. and 15 mg b.i.d. Significant improvement was found in the gait scores and in the total disability scores in the high dose group (p less than 0.05). In addition, there was a trend toward improvement, though not significant, in the bradykinesia and rigidity scores in the high dose group and in the disability scores in the low dose group. Four patients in the low dose group and five patients in the high dose group decreased their Sinemet doses while no patients increased their Sinemet dose. There were no adverse effects observed in this study. These findings suggest that ciladopa may be an efficacious agent in Parkinson's disease. The low incidence of adverse effects with this agent suggests that higher doses may be utilized and may prove to be more effective.
 ...
PMID:A double-blind evaluation of ciladopa in Parkinson's disease. 333 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>