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)

Five patients with advanced Parkinson's disease and fluctuations in therapeutic response to levodopa participated in, and four completed, an open label study of the efficacy of Sinemet CR5. Reductions in the number of daily doses and "off" periods as well as the increase in interdose interval and percent "on" time versus standard Sinemet were comparable to those achieved with Sinemet CR4 in these same patients. As compared with Sinemet CR4, there was a greater delay in the occurrence of peak plasma levodopa concentrations, and relative bioavailability was reduced. Sinemet CR5 appears to offer no advantages over Sinemet CR4 in the treatment of response fluctuations in Parkinson's disease.
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PMID:Controlled-release levodopa/carbidopa. III: Sinemet CR5 treatment of response fluctuations in Parkinson's disease. 337 25

To clarify the influence of gastric emptying on levodopa-related motor fluctuations in Parkinson's disease, we assessed mobility and plasma levodopa concentrations in 10 patients during five modes of levodopa administration: (1) standard intermittent oral (SIO), (2) intermittent duodenal (ID), (3) continuous duodenal infusion (CDI), (4) continuous gastric infusion (CGI), and (5) controlled-release Sinemet (CR-4). The rank order from greatest to least for both percentage of time "on" and average mobility score was CDI, CGI, ID, CR-4, and SIO. The rank order for variance of means, a measure of fluctuation, from least to greatest for mobility was CDI, CGI, CR-4, ID, SIO, and for plasma levodopa concentrations was CDI, CGI, ID, SIO, and CR-4. The results demonstrate that it is possible to produce very steady plasma concentrations of levodopa with a corresponding reduction in motor fluctuations by continuous intraduodenal administration of the drug. This mode of delivery is an ideal model for the development of optimal continuous-release preparations of levodopa. Other enteral routes have produced a more variable plasma levodopa concentration and clinical response.
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PMID:Duodenal and gastric delivery of levodopa in parkinsonism. 340 40

In this open study patients with advanced Parkinson's disease, who experienced pronounced fluctuations in symptoms while on standard L-dopa, were switched from Madopar/Sinemet to Madopar HBS. The dosage was adjusted until optimal response was obtained. The effect was unsatisfactory in 4 cases and side effects intervened in another 2. The remaining 16 patients exhibited substantial and frequently significant improvements with regard to both akinetic and dyskinetic phenomena. L-Dopa dosage was increased in all cases, and addition of standard L-dopa was required in one third of the cases. These benefits continued in the majority of patients.
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PMID:Madopar HBS: slow-release levodopa and benserazide in parkinsonian patients presenting marked fluctuations in symptoms on standard L-dopa treatment. 342 10

Parkinsonian patients may have symptoms consistent with intestinal pseudo-obstruction, but a primary intestinal abnormality has not been shown. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), after conversion to a toxic metabolite via the monoamine oxidase system, can induce Parkinson's disease by destroying dopaminergic neurons in the substantia nigra in humans and primates. Rodents have some catecholamine depletion but much less so than primates. Using chronic bipolar electrodes on the proximal jejunum of Wistar rats, we show significant, chronic migrating myoelectric complex disruption (P less than 0.001) and prolongation of irregular spike activity (P less than 0.001). Pargyline (a monoamine oxidase inhibitor) pretreatment significantly blocked these myoelectric changes. Sinemet (L-dopa and carbidopa), given after MPTP to replete dopamine, decreased the MPTP-induced migrating myoelectric complex disruption. Jejunal myenteric plexus dopamine levels were significantly decreased (to 61% of control) after MPTP but after much higher doses than were required to disrupt migrating myoelectric complex activity (180 mg/kg total vs. 30 mg/kg). Dopamine in the central nervous system was not depleted. We conclude that MPTP causes intestinal myoelectric disruption (which can be blocked by pargyline and decreased by Sinemet) possibly through enteric, but not central, nervous system effects.
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PMID:Chronic alterations in jejunal myoelectric activity in rats due to MPTP. 350 Dec 48

Two patients with Parkinson's disease presented with unprovoked, abrupt onset of hallucinations, confusion and the simultaneous worsening of parkinsonian symptoms. This clinical syndrome appears to be a rare complication of dopaminergic therapy since improvement occurred gradually with reduction of Sinemet dosage.
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PMID:Sudden onset of confusion with severe exacerbation of parkinsonism during levodopa therapy. 350 49

Ciladopa is a partial dopamine agonist that is effective in patients with advanced Parkinson's disease who are no longer satisfactorily responding to levodopa. Thirty-one patients participated in a double-blind randomized study of ciladopa (added to levodopa) versus placebo. Among 21 patients randomized to treatment with ciladopa and levodopa, there was a 32% decrease in symptoms on the Modified Columbia University Disability Scale. This change was significant, p less than or equal to 0.05. Eight of the 21 patients (38%) improved by at least 50%. The mean number of hours "on" increased by 20%. This change was significant, p less than or equal to 0.05. Five of the 21 patients (24%) were on for at least 4 hours more than at baseline. Dyskinesias were not increased. The mean dose of ciladopa was 19.5 mg/d. The mean dose of levodopa in Sinemet was decreased by 10%. Studies with ciladopa in humans had to be discontinued because of the occurrence of microscopic testicular tumors in some rodents. Although improvement in patients taking ciladopa was modest, there were few adverse effects. These results are encouraging, because two other partial agonists are now available, and they may be as effective as ciladopa.
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PMID:Advanced Parkinson's disease: use of partial dopamine agonist, ciladopa. 357 92

Long-acting levodopa/carbidopa combination (CR-4-Sinemet) was compared with traditional levodopa/carbidopa (Sinemet) open label in 20 patients with Parkinson's disease and "wearing-off" phenomena. After 4 to 6 weeks of therapy with CR-4-Sinemet, the number of daily doses of medication dropped significantly compared with traditional Sinemet, disability improved, and "on" time increased. In nine patients receiving CR-4-Sinemet for 3 months, the number of daily doses and the on time without chorea remained significantly improved. CR-4-Sinemet peaked in plasma after 2 hours, and moderately high levels remained at 4 hours after the dose. Side effects were similar between traditional Sinemet and CR-4 Sinemet.
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PMID:Parkinson's disease and motor fluctuations: long-acting carbidopa/levodopa (CR-4-Sinemet). 357 96

Motor fluctuations and non-response to carbidopa-levodopa (Sinemet) therapy are major problems in the long-term management of Parkinson's disease. Levodopa manipulation, addition of adjuvants, and drug holidays are often unsuccessful. Others have shown that the clinical state of stabilized Parkinsonians can be reversed with intravenous administration of large neutral amino acids. Reasoning that dietary protein might precipitate motor oscillations and non-response, a low-protein daytime diet (7 g) was offered to fifteen patients. Eighty-six percent of this sample demonstrated immediate sensitivity to Sinemet. While on a low-protein diet, patients' clinical function was predominantly choreatic. Eight patients required a 10-60 percent reduction in their daily levodopa dose in order to minimize this choreatic tendency. Discontinuation of adjuvants did not compromise motor independence. Conversely, while on a high-protein diet (160 g), patients were predominantly immobile with markedly elevated plasma amino acid and levodopa levels. Consequently, elimination of dietary protein from breakfast and lunch can offer an effective and easily modified method for the amelioration of motor fluctuations and non-response to Sinemet in Parkinson's disease during working hours.
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PMID:Dietary method for reducing fluctuations in Parkinson's disease. 357 10

Sixteen patients with Parkinson's disease and therapeutic response fluctuations entered an open-label trial of a controlled-release carbidopa/levodopa preparation, Sinemet CR4. Sinemet CR4 behaved as a slow release preparation. At the end of 6 weeks CR4 treatment, there was an increase in percent "on" time and mean interdose interval; the number of daily doses and "off" periods were diminished and a slight reduction in the variability of plasma levodopa levels was observed. Overall benefit waned over the next 6 months, despite addition of standard levodopa or Sinemet to overcome the delayed onset of antiparkinsonian effect of CR4 which resulted from prolongation in the Tmax for levodopa. The major benefits of CR4 were reduction in off time and in the number of daily off periods, with fewer levodopa doses per day and prolongation of the interdose interval.
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PMID:Controlled-release levodopa/carbidopa. II. Sinemet CR4 treatment of response fluctuations in Parkinson's disease. 365 64

A 60 year old woman with idiopathic Parkinson's disease had been prescribed thioridazine for schizophrenia. Five months after this was stopped, Sinemet also considered of dubious therapeutic value, was withdrawn. One week later she developed features of the neuroleptic malignant syndrome (NMS) accompanied by myoglobinuric renal failure. Post-mortem examination confirmed Lewy body degeneration in the substantia nigra. It is proposed that NMS may be caused by levodopa withdrawal in Parkinson's disease, and that it is withdrawal of dopaminergic drive that causes the syndrome.
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PMID:Levodopa withdrawal syndrome identical to neuroleptic malignant syndrome. 379 65


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