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)

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

Lergotrile mesylate, a direct-acting dopamine agonist, was administered for up to 10 months to 25 patients with Parkinson disease. Of six patients not receiving levodopa concurrently, five showed definite improvement in parkinsonian signs and symptoms. These results are the first clear indication that lergotrile is efficacious, independently of any interaction with levodopa, in the treatment of Parkinson disease. The drug was also effective in relieving some complications of long-term levodopa therapy. Lergotrile was more effective in alleviating on-off problems than in reversing loss of levodopa efficacy. Side effects of lergotrile included exacerbation of hallucinations, dyskinesias, hypotension, and alterations in liver function tests.
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PMID:Lergotrile in the treatment of parkinsonism. 56 68

Lergotrile, an ergot alkaloid, has been shown to be effective in treating disorders associated with elevated serum prolactin levels (e.g., galactorrhea-amenorrhea). Lergotrile has also been found to be a potent dopaminergic agonist and thus to be effective in Parkinson's disease. This study describes the physiologic disposition of lergotrile after administration to human volunteers. N-14CH3-lergotrile was rapidly absorbed from the gastrointestinal tract. Lergotrile was detected at low concentrations in plasma when subjects received large doses over extended periods of time. The major portion of radioactivity in plasma was attributed to the presence of circulating metabolites of lergotrile. Lergotrile metabolities were eliminated in the feces (ca. 60%), urine (ca. 20%), and breath (ca. 7% as 14CO2). A metabolite in feces was identified as 13-OH-lergotrile (up to 30% of the dose). A metabolite in urine was formed by conversion of the C8-acetonitrile group of lergotrile to a carboxyl group (about 10% of the dose). The presence of 14CO2 in the expired air after administering N-14C-methyl-lergotrile indicated that the drug was N-demethylated to form norlergotrile.
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PMID:Physiologic disposition of lergotrile. 62 32