Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lergotrile was administered to 53 patients with advanced Parkinson disease (PD), who had increasing disability despite optimal treatment with levodopa/carbidopa (Sinemet). Thirty-nine patients who could tolerate at least 20 mg per day lergotrile (thus considered "adequately treated") had significant descreases in rigidity, tremor, bradykinesia, gait disturbance, and total score without increased involuntary movements. Twenty-one of these 39 patients improved by at least one stage. Among the 39 patients, 23 had "on-off" effects, and in 13 of these the "on-off" effects decreased on lergotrile. The mean daily dose of lergotrile in adequately treated patients was 49 mg, permitting a 10 percent reduction in the dose of levodopa. Lergotrile was discontinued in 33 of the 53 patients because of adverse effects, including hepatotoxicity (11 patients), mental changes (12 patients) and orthostatic hypotension (8 patients). Although lergotrile, when added to levodopa, has a definite antiparkinsonian effect, the incidence of adverse effects, particularly hepatotoxicity, makes it unlikely that this ergot alkaloid will become widely available for the treatment of PD. Analogues of lergotrile have been synthesized, and it is hoped that they will duplicate the antiparkinsonian effect of this drug without its toxicity.
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PMID:Lergotrile in Parkinson disease: further studies. 3 8

An experimental anticholinergic drug, elantrine, had shown significant improvement in tremor of parkinsonism in 89 patients not taking L-dopa. A double-blind study of 22 parkinsonian patients stabilized on L-dopa showed marked improvement in tremor and moderate improvement in rigidity and bradykinesia when elantrine was added to their treatment program. Nine of 15 patients taking L-dopa (or Sinemet) and elantrine had cessation of all tremor and have continued free of tremor to date, over two years.
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PMID:Evaluation of an experimental anticholinergic drug, elantrine, in treating the tremor of parkinsonism. 33 73

Bromocriptine was administered to 66 patients with advanced Parkinson disease (PD) and increasing disability despite optimal treatment with levodopa/carbidopa (Sinemet). Forty-five patients tolerated at least 25 mg per day of bromocriptine (the "adequately treated" group) in addition to Sinemet and had significantly decreased rigidity, tremor, bradykinesia, gait disturbance, and total score, but increased involuntary movements. Twenty-five of these 45 patients improved by at least one stage. Among the 45 patients, 27 had "on-off" effects, and in 19 the "on-off" effects decreased on bromocriptine. The mean dose of bromocriptine in adequately treated patients las 47 mg, permitting a 10 percent reduction in the dose of levodopa. Twelve adequately treated patients received bromocriptine for at least 1 year, and 8 continued for longer than this. Bromocriptine was discontinued in 29 of 66 patients because of adverse effects, including mental changes (14 patients) and involuntary movements (9 patients). All adverse effects were reversible. Despite adverse effects, expense, and scarcity, bromocriptine, when added to levodopa, is useful in patients with advanced disease who no longer respond satisfactorily to levodopa, and for whom no other treatment is available.
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PMID:Bromocriptine in Parkinson disease: further studies. 57 81

On the basis of observations of 18 patients the authors evaluated clinically the action of Sinement preparation (Merch, Sharp and Dohme) containing L-dopa 250 mg and carbidopa 25 mg in the treatment of Parkinson's disease. In the evaluation particular attention was given to side effects. Therapeutic results of Sinemet and L-dopa alone were compared in patients receiving these drugs alternatively. The observations of authors indicate that Sinemet gives the same therapeutic results as L-dopa, but in much lower doses and with less frequent side effects. Sinemet, similarly as L-dopa exerts the best effect on bradykinesia and muscular rigidity and less on tremor.
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PMID:[Comparison between results achieved by administering L-dopa and Sinemet in parkinsonism in the light of our records]. 118 52

Parkinson's disease affects thousands of Americans, men and women equally and apparently with little regard to race. Its diagnosis depends largely on repeated clinical observations of representative signs, such as resting tremor, rigidity, bradykinesia, and gait disturbances. Patients progress through stages: Early disease involves only one limb or side and confers minimal disability, but advanced disease restricts patients to full care. Treatment is chosen on the basis of disease stage and patient response. Combination carbidopa-levodopa (Sinemet) is appropriate for any significant degree of disability, and other antiparkinsonian drugs and anticholinergic agents may be used as adjuncts. Electroconvulsive therapy, use of selegiline hydrochloride (Eldepryl), and surgery are still undergoing investigation but may hold promise.
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PMID:Treating the progressive stages of Parkinson's disease. 190 7

It has been proposed that initiation of anti-Parkinson therapy with continuous release formulations of Sinemet might prevent or delay the development of adverse effects associated with chronic levodopa therapy employed in standard formulations. In anticipation of a prospective study comparing Sinemet to Sinemet CR in previously untreated Parkinson's disease patients, we evaluated Sinemet CR as primary therapy in 45 levodopa-naive Parkinson's disease patients in a 12 week, open-label, multi-center study. At the conclusion of the study, optimal results were obtained with levodopa administered as Sinemet CR in a total daily dose of 497 mg divided into 2.4 doses per day. Statistically significant improvement compared to baseline was observed for total Parkinson's score as well as each of rigidity, tremor, bradykinesia, gait and postural stability. Statistically significant improvement was also noted in total disability as well as in each of its components. Adverse experiences were mild and transient and no significant laboratory abnormalities were encountered. We conclude that a daily dose of 1 to 1.5 tablets b.i.d. of Sinemet CR as primary therapy for patients with Parkinson's disease is well tolerated and provides effective therapy.
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PMID:An open multicenter trial of Sinemet CR in levodopa-naive Parkinson's disease patients. 207 Mar 63

DL-threo-3,4-dihydroxyphenylserine (DL-threo-DOPS) was administered during 10 days to 4 patients with longstanding Parkinson's disease in addition to their treatment with L-3,4-dihydroxyphenyl-L-alanine (L-DOPA)-carbidopa (Sinemet). All patients tended to improve in their symptoms freezing, all day life activity and mood. There were no improvements in rigidity, tremor, and akinesia (in general). During the DL-threo-DOPS-treatment cerebrospinal fluid (CSF), serum and urine concentrations of catecholamines were measured. The results show that DL-threo-DOPS is transported to the brain and CSF in a way comparable with L-DOPA. However, no measurable increase of 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG) in CSF could be demonstrated. This suggests that the synthesis of noradrenaline from DL-threo-DOPS in the brain is doubtful. In addition measurements in urine reveals that at the dose used Sinemet prevents peripheral decarboxylation of DL-threo-DOPS into noradrenaline. Other possible metabolic pathways of DL-threo-DOPS are discussed.
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PMID:Catecholamine metabolism during additional administration of DL-threo-3,4-dihydroxyphenylserine to patients with Parkinson's disease. 247 57

A 42-year-old woman suffered unexplained weight loss followed by action tremor and difficulty initiating gait. Three months after onset of symptoms, infiltrating ductal carcinoma of the breast, metastatic to liver and lymph nodes, was diagnosed and treated briefly with cyclophosphamide, methotrexate, and 5-flourouracil (5FU). Severe symmetric action and postural tremor with a myoclonic component developed, with minimal rest tremor, severe dysarthria and dysphagia, small-stepped and slightly ataxic gait progressing to a bedbound state, and severe widespread dystonic posturing. The latter began as a typical parkinsonian posture of trunk and upper extremities and progressed to a fixed and painful flexion of the elbows and wrists and extension of fingers and neck. Sinemet, anticholinergics, baclofen, diazepam, and plasmapheresis gave no benefit. The patient died of complications of immobility 5 months after neurologic symptom onset. Autopsy revealed many pigment-laden macrophages in substantia nigra and moderate loss of pigmented neurons. Inflammation, Lewy bodies, and tumor were absent. Cerebellar Purkinje cells were moderately depleted. Mild neuronal loss and gliosis were present in globus pallidus and cerebellar cortex. Stains for anti-human IgG, IgM, kappa, and lambda were negative. This, to our knowledge, is the first report of paraneoplastic degeneration of substantia nigra or paraneoplastic parkinsonism.
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PMID:Paraneoplastic degeneration of the substantia nigra with dystonia and parkinsonism. 254 19

The efficacy of controlled-release Sinemet was evaluated in a 52-week open trial involving 20 patients (14 men, 6 women; mean age 66 years, range 56 to 82) with idiopathic Parkinson's disease of 8 years' mean duration. The mean daily dosage of levodopa was 662.5 mg (200 to 1600 mg) on entering the study and 800 mg (200 to 2400 mg) after 52 weeks. The mean number of daily doses was reduced from 5.0 (2 to 16) at entry to 3.3 (1 to 6) after 52 weeks. Rigidity, tremor, and bradykinesia were scored at 3 intervals during baseline and 8 intervals during the study on controlled-release levodopa. All parameters improved, with maximum improvement seen at week 12. Side effects were less frequent on the controlled-release preparation. After 5 months, 1 patient developed protracted dyskinesia with freezing episodes and end-of-dose deterioration on dose frequency reduction.
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PMID:Sinemet CR in the treatment of patients with Parkinson's disease already on long-term treatment with levodopa. 258 67

Twenty-one patients with Parkinson's disease and motor fluctuations who completed a double-blind study comparing controlled-release carbidopa/levodopa (Sinemet CR4) with standard Sinemet (SS) were evaluated one year following completion of the study. Five patients remained on CR4 alone; 16 continued on CR4 plus SS, and one also required addition of bromocriptine. Patients were significantly worse (p less than 0.05) at one year compared with double-blind CR4 phase (DBCR) for nine parameters of the motor exam, six activities of daily living (ADL), Hoehn & Yahr staging, and physician's global assessment. Compared with baseline SS, patients were worse at one year for four points of the motor exam, two of mentation, behavior, and mood, and 11 parameters of ADL. Improvement at one year was noted for less action and postural tremor and decreased duration of dyskinesias for both comparison periods. There was elimination of early morning dystonia at one year over the DBCR period and more hours "on" without dyskinesias and fewer hours "on" with dyskinesias compared with baseline SS. Total levodopa dosage was not significantly changed over the year. These data suggest that, in long-term use, CR4 remains more efficacious than SS alone for Parkinson's patients experiencing motor fluctuations, although disease progression continues despite optimal medication.
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PMID:Long-term efficacy of controlled-release carbidopa/levodopa in patients with advanced Parkinson's disease. 269 Jul 30


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