Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0233565 (bradykinesia)
 2,352 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

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

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

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 paper is concerned with a study of the effect of metamizil in 45 patients with different forms of vascular parkinsonism. It was established that metamizil exerts a positive effect on the development of neurological symptoms (rigidity, bradykinesia, tremor) in mild and moderately expressed degrees of lesions. In most of the cases the drugs appeared effective in doses of 0.001 g thrice daily, and in separate cases 0.001 g 6 times daily. In the majority of patients metazil was tolerated without significant side effects. In some patients the side effects (vertigo, dryness in the mouth) were slightly expressed. The effect of treatment was seen after 2 days up to 2 weeks and lasted during the whole course of treatment and sometimes after it. Metamizil possessing a moderate sedative action, as well as spasmolytical and hypotensive is indicated for patients with vascular parkinsonism.
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PMID:[Experience in treating vascular parkinsonism with metamysil]. 64 11

Postural or Parkinson-like tremor, which results from the impairment of mechanisms which are predominantly lateralized in the brain, is most likely related to the combined impairment of the dopaminergic nigrostriatal pathway and the corresponding rubro-olivo-cerebello-rubral loop (without excluding the possiblity that other nervous mechanisms interconnected with these structures may represent an alternative disturbance). The integrity of the internal division of the pallidum and the ventrolateral area of the thalamus and their efferent fibers as well as the motor cortex and certain of its cortico-subcortico-spinal pathways (Figures 1 and 2) is apparently an essential feature for the elaboration of the rhythmic bursts associated with the appearance of postural tremor. The integrity of the spinal sensory roots and the rubro-tegmentospinal tract is not a prerequisite for the expression of postural tremor, a condition which seems essential for the production of rigidity. The latter facts suggest that the disturbances which subserve these two types of motor impairment, often concomitantly present in Parkinsonism, partially involve the impairment of different mechanisms although the loss of the DA fibers originating in the substantia nigra and ending in the neostriatum (Figure 1) appears to represent a disturbance common to both types of disorders. Bradykinesia which may be associated with an impairment of catecholamine metabolism (and more especially the neostriatal DA mechanisms) on both sides of the brain may also result from bilateral lesions of the pallidum or of its outflow corresponding, in the main, to the pallidothalamic fibers ending in the ventrolateral thalamus. The latter types of lesion most likely exclude the influence of the monoaminergic, cholinergic and gabaminergic activities normally originating in the striopallidal system and influencing the activity transmitted to other CNS mechanisms. Severe akinesia, however, apparently depends on more profound and generalized disturbances of brain monoamine metabolism with or without the involvement of other ill-defined mechanisms. At any rate the impairment of the brain DA mechanisms (and especially those of the neostriatum) seems to represent a major feature in the production of the Parkinsonian type of akinesia. Further work is needed to establish the relative importance of the loss of catecholaminergic mechanisms other than those of the neostriatum in the production of akinesia.
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PMID:Physiopathology of experimental Parkinsonism in the monkey. 80 27


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