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)

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

Bromocriptine and lergotrile were administered to 81 patients with Parkinson disease (PD) and increasing disability despite optimal treatment with levodopa (secondary levodopa failures). Sixty-six patients were treated with bromocriptine and 53 patients were treated with lergotrile. Both groups had significantly decreased rigidity, tremor, bradykinesia and gait disturbance upon addition of bromocriptine or lergotrile to levodopa. Twenty-five patients improved at least one-stage on bromocriptine, and 21 improved at least one-stage on lergotrile. The mean dose of bromocriptine was 47 mg, and the mean dose of lergotrile was 49 mg, permitting a 10% reduction in levodopa. Bromocriptine was discontinued in 29 of 66 patients because of adverse effects, including mental changes (14 patients) and involuntary movements (9 patients). Lergotrile was discontinued in 33 of 53 patients because of adverse effects including hepatotoxicity (11 patients) and mental changes (12 patients). The results of treatment with bromocriptine or lergotrile were comparable, with patients either responding or not. Bromocriptine will shortly be available for use in PD. Lergotrile, because of the hepatotoxicity, will not.
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PMID:Treatment of Parkinson's disease with dopamine agonists: a review. 3 52

The antiparkinsonian activity of lergotrile mesylate, a presumed dopaminergic receptor stimulating agent, was investigating in monkeys with surgically induced tremor and in parkinsonian patients. The administration of lergotrile resulted in a dose-dependent reduction in the intensity of tremor in the monkeys. In 13 patients with Parkinson's disease treated with lergotrile (up to 12 mg a day), overall improvement was observed in five. Tremor was the main clinical feature to benefit, and the improvement reached statistical significance. In a subgroup of four patients treated with a higher dose of lergotrile (up to 20 mg a day), further improvement in rigidity and bradykinesia was noted, but again, only improvement in tremor was statistically significant. Adverse effects included orthostatic hypotension, behavioral alterations, and nausea and vomiting. These were severe enough to result in drug withdrawal in three patients.
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PMID:Studies on the antiparkinsonism efficacy of lergotrile. 16 32

Lergotrile mesylate, an ergot alkaloid derivative and putative dopamine agonist, was effective in the majority of patients with Parkinson's disease who were showing signs of disease progression despite treatment with levodopa combined with a peripheral decarboxylase inhibitor (carbidopa). Among 20 patients completing a six-month trial, there was a significant (P less than .01) reduction in rigidity, tremor, bradykinesia, gait disturbance, and total score when lergotrile was added to levodopa plus carbidopa. Mean daily dose of lergotrile mesylate was 52 mg, and the mean daily dose of levodopa was reduced by 15%. Abnormal involuntary movements were decreased on addition of lergotrile and reduction in levodopa while mental changes and orthostatic hypotension were increased. Elevations in serum transaminase levels were noted in three patients. The ergot alkaloids promise to be an important new class of antiparkinsonian drugs.
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PMID:Treatment of Parkinson's disease with lergotrile mesylate. 33 94

In a study of 16 psychotic patients with neuroleptic-induced tardive dyskinesia and 16 patients with Parkinson's disease and L-Dopa-induced hyperkinesia it was found that (1) tardive dyskinesia, compared to L-Dopa hyperkinesia, was localized almost exclusively to the oral region (P mean value of 0.01), whereas theL-Dopa hyperkinesia was more pronounced in the neck (P mean value of 0.05) and the extremities (P mean value of 0.05); (2) L-Dopa hyperkinesia showed an increasing tendency to oral preponderance with age, irrespective of the severity ofParkinsonism and extra-oral hyperkinesia, while tardive dyskinesia only itensified with age, without any change in distribution; and (3) extra-oral L-Dopa hyperkinesia was related to the localization and severity of pretreatment Parkinsonism, and more to bradykinesia than to rigidity and tremor. It is concluded that the irreversible neurotoxic effect of neuroleptic drugs may be associated with age-related changes in the oral somatotopic region of the basal ganglia (to be given consideration in any future search for the pathogenetic process underlying irreversible tardive dyskinesia), and that the pathophysiology of involuntary hyperkinesia in neuroleptic-treated psychiatric patients and in L-Dopatreated parkinson patients may consist of a primary dopamine deficiency (pharmacological or structural), and a secondary relative hyperactivity in the dopaminergic system ("dopaminergic hypersensitivity") possibly corresponding to hypoactivity in the cholinergic system.
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PMID:Relationship between tardive dyskinesia, L-Dopa-induced hyperkinesia and parkinsonism. 40 41

Ocular movement was studied in 19 patients with Parkinson's disease and in ten normal controls. Common abnormalities included "hypometric saccade" on the eye-tracking test and on command, "saccadic pursuit," and convergence paresis. Reaction time was longer in patients with Parkinson's disease than in controls for horizontal saccadic gaze, finger movements, and body movements. Maximal saccadic velocity of horizontal gaze was slower in patients with Parkinson's disease than in controls. Slowing of the horizontal saccadic movement correlated significantly with an increased reaction time of finger and body movements. Correlation of decreased saccadic velocity with increased reaction time of finger movement was found for the finger ipsilateral to the direction of horizontal gaze, but not for the contralateral finger. It is postulated from these facts that bradykinesia also exists in eye movements in Parkinson's disease.
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PMID:Oculomotor abnormalities in Parkinson's disease. 45 34

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

Patients with Parkinson's disease performed several different stereotyped elbow flexion tasks, and the electromyographic (EMG) patterns from biceps and triceps were compared with previously established normal standards. The EMG pattern during a smooth flexion task was almost always abnormal and was characterized by alternating activity in biceps and triceps. The EMG patterns during a fast flexion task were also usually abnormal although they were always composed of bursts of EMG activity of normal duration appearing alternately in the agonist and antagonist muscles. These bursts, associated with movements of the limb, have a superficially similar appearance to the EMG bursts seen with tremor-at-rest, but certain physiological differences are demonstrated. This study demonstrates that both slow (ramp) and fast (ballistic) movements are clearly abnormal in these patients with disease of the basal ganglia. In a task designed to investigate antagonist inhibition before agonist activity, a majority of the patients performed normally. This suggests that, contrary to previous claims, slowness of movement (akinesia/bradykinesia) is not due either to failure to relax or to rigidity of antagonist muscle.
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PMID:Analysis of stereotyped voluntary movements at the elbow in patients with Parkinson's disease. 59 80

The electrical activity of single motor units was recorded from the first dorsal interosseous muscles of nine patients with Parkinson's disease. Six of these patients had a combination of the following abnormal motor unit properies: (1) a variable delay period of 20 seconds to 3 minutes between the initiation of voluntary effort and the recruitment of the first group of motor units; (2) after recruitment, some of the motor units stopped firing for durations of 10s, 40s, 75s... 3 min.; (3) some of the motor units fired at abnormally low frequencies of 2-3 per second. All these six patients had slowed finger movement, and five of the six were studied while off levodopa for two to seven days. One of these patients, reinvestigated after levodopa therapy had been restarted, demonstrated improvement in motor unit control. The three remaining patients who were studied while on uninterrupted levodopa therapy could make rapid finger movements, could recruit motor units without delay, and could fire recruited motor units continuously at normal frequencies of 6-14 per second. These results suggest that levodopa therapy is effective in Parkinson's disease at least partly because of its ability to correct abnormalities in the recruitment of motor units. Levodopa also corrects the abnormal motor unit firing pattern. The abnormal motor unit properties found in these patients could account for some aspects of bradykinesia.
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PMID:Electrical properties of motor units in Parkinsonism and a possible relationship with bradykinesia. 76 83

The occurence of extranuchal dystonia, facial spasm, parkinsonian symptoms (facial masking, bradykinesia, rigidity), tremor and family history of tremor was tabulated in a group of 30 patients with IST. The incidence of extranuchal dystonia increased as severity of IST increased. There was a strong trend for severity of extranuchal dystonia to increase as severity of torticollis increased, which was significant (p less than 0.001). There was a similar trend for severity of facial spasm to increase with increasing severity of torticollis (p less than 0.025). Parkinsonian features were seen in 10 of 30 patients, and in three the diagnosis of Parkinson's disease could be entertained. Tremor was seen in 26 of 30 patients being mild in 12, moderate in 11, and severe in three. A family history of tremor was present in 16 of 28 cases for whom history was available (12 primary, four secondary relations). The results are most consistent with the hypothesis that IST is a variant of DMD with tremor as an integral part of the disease and tremor represents a forme of the disease in family members.
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PMID:Dystonia and tremor in spasmodic torticollis. 94 73


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