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)

We treated 20 early Parkinson's disease subjects with the dopamine agonist lisuride in combination with the MAO-B inhibitor selegiline (L-deprenyl). We started with lisuride alone for one month, then we added selegiline versus placebo to lisuride in double-blind conditions for 3 months; finally all patients received lisuride and selegiline for another 3 months. Lisuride alone (1.43 +/- 0.10 mg) significantly improved PD. When selegiline (10 mg/day) was added in the double-blind phase the mean lisuride dosage could be reduced by 22.8% without deterioration of the clinical effects, and the same occurred in the former placebo group when selegiline was added. The combination of both drugs was well tolerated. These data are of interest for the interpretation of the effects of selegiline.
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PMID:Lisuride plus selegiline in the treatment of early Parkinson's disease. 190 85

We studied the effect of intracerebroventricular infusion of dopamine and dopamine agonists in rat and primate models of Parkinson's disease as an experimental approach to the treatment of levodopa-induced fluctuations. The infusion of dopamine, lisuride, and pergolide into the ventricle ipsilateral to the lesion, by 6-hydroxydopamine, of the nigrostriatal pathway induced a contralateral rotation which was maximal 24-48 h after infusion and whose intensity progressively decreased over the period of 1 week. [3H]Spiperone binding was decreased by the infusion of dopamine but the responses to subcutaneous apomomorphine were unchanged. The infusion of dopamine also restored the levels of monoamines in the rat brain. In chronic reserpized rats, the infusion of dopamine restored brain levels of dopamine but did not reverse akinesia unless monoamine oxidase inhibitors were simultaneously administered, either systemically or intracerebroventricularly. Lisuride and pergolide proved much weaker than dopamine in reversing the effects of reserpine. Intracerebroventricular infusion of dopamine plus deprenyl reversed MPTP induced akinesia in monkeys but the pump used for the delivery was not well tolerated, because of its size, by the animals.
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PMID:Continuous intracerebroventricular infusion of dopamine and dopamine agonists through a totally implanted drug delivery system in animal models of Parkinson's disease. 290 48

Four patients with Parkinson's disease and severe fluctuating responses to levodopa and oral dopamine agonists were treated with continuous administration of lisuride infusions, administered by means of an externally worn pump. Levodopa dosage ranged from 300 to 687 mg/day and was kept stable throughout the study. In addition increasing doses of lisuride were injected subcutaneously in the abdomen. Lisuride doses ranged from 41 to 104 micrograms/h. A marked improvement in mobility was observed in every patient while severe biphasic dyskinesais almost remitted in one of them. The most common side-effect was the presence of subcutaneous nodules appearing at the injection site. Two cases had mild hemorrhagic complications and one initially had nausea. One patient developed acute psychiatric disturbances severe enough to be excluded from the study. Our findings suggest that lisuride subcutaneous infusions can be useful in severily handicapped parkinsonian patients, however local and psychiatric side-effects may be a serious threat in the long-term care.
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PMID:Treatment of Parkinson's disease with subcutaneous lisuride infusions. 296 54

Lisuride, a semisynthetic dopaminergic ergot derivative, was administered in 34 patients with Parkinson's disease (mean age 67.5 years, average duration of illness 7.1 years, mostly stage IV) in an average oral dosage of 1.2 to 1.5 mg (range 0.4 to 3.0 mg) in addition to basic treatment with levodopa and decarboxylase inhibitor. Duration of combined treatment was 3 to 44 months. Daily dose of levodopa could be reduced by 13 to 34%. In the short-term group (3 months) the total disability score improved by 50%, and in the long-term group (up to 44 months) by 46%, with improvement of rigidity, tremor, speech and repeated movements, less of bradykinesia. Similar to treatment with dopamine agonists, after 18 to 24 months, despite increased dosage of levodopa, a slight increase of some clinical features of parkinsonism, particularly bradykinesia and gait disorders, were observed. Daily fluctuation and on-off symptoms often improved in intensity, but were eliminated only in a small number of patients. Discontinuation of lisuride due to adverse effects was necessary in 17.6%. Often, however, preexisting adverse effects of levodopa therapy, particularly psychiatric complications, responded favorably. Lisuride is a new effective agent in the combination treatment of advanced stages of parkinsonism.
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PMID:[Lisuride in the combination treatment of Parkinson disease]. 311 Oct 99

On-off fluctuations in longstanding Parkinson's disease initially respond well to a combined drug regime of Levodopa with direct dopamine agonists and L-deprenyl. L-Dopa infusions are efficient, but not applicable for longer use. S.c.-Lisuride-infusions reduce markedly motor-response fluctuations, dystonias and hyperkinesias, but bear the risk of inducing confusion or even psychosis. In patients with coexisting response fluctuations and psychiatric disturbances a therapeutic approach is outlined to preserve still some favourable effects on motor performance avoiding severe psychosis. Side-effects and possible complications of that therapy are discussed as are some further indications for the clinical use of Lisuride in akinetic crisis, the neuroleptic malignant syndrome and in dyskinesias.
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PMID:Chronic s.c. lisuride in Parkinson's disease--motor-performance and avoidance of psychiatric side effects. 316 38

The continuous dopaminergic stimulation provided by infusion of dopamine agonist drugs, is a very effective strategy to control ON-OFF fluctuation in Parkinson's disease. Lisuride is a potent dopamine agonist drug, very soluble in water and can be administered subcutaneously. Many authors have shown that the subcutaneous infusion of lisuride can control fluctuations when applied in combination with oral levodopa as a 24 hour continuous infusion regimen. In this study, lisuride was given without any other antiparkinsonian medicament and using a 12 hour infusion regimen wherever possible. 13 fluctuating Parkinsonian patients were studied. 6 out of these 13 were satisfactory treated with lisuride alone and the remaining 7 with a combination of Lisuride + oral levodopa. Only in 3 out of 13 patients the 24 hour infusion regimen was required.
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PMID:Subcutaneous lisuride infusion in Parkinson's disease: clinical results using different modes of administration. 316 37

L-Dopa is still the most effective drug for the treatment of Parkinson's Disease, but after 5 years or more of therapy fluctuations in motor performance and abnormal involuntary movements commonly appear. Continuous intravenous infusions of L-Dopa abolish or strikingly reduce such fluctuations. Unfortunately, this is not suitable for daily treatment because of the low solubility of L-Dopa. Lisuride is a potent dopamine agonist and is very soluble in water. In this study the clinical effects of L-Dopa and lisuride continuous intravenous infusions were compared in a group of 20 fluctuating parkinsonian patients. L-Dopa controlled fluctuations in almost all the subjects, whereas only seven patients were continuously mobile while taking lisuride. Another seven patients showed a fluctuating response and the remaining six did not satisfactorily respond to lisuride. Dyskinesias were present in all patients during "on" phases, with both levodopa and lisuride treatment.
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PMID:Comparison between L-dopa and lisuride intravenous infusions: a clinical study. 321 Nov 76

Lisuride at a mean daily dose of 3.2 mg was given to 15 untreated idiopathic Parkinson's disease patients. There were 10 dropouts, due mainly to inefficacy in the first months of therapy. The parkinsonian pattern in the patients who remained in the study for the full 4 years showed distinct improvement, which was maintained for less than 2 years. The patients did not develop "on-off" phenomena or abnormal involuntary movements during follow-up.
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PMID:Lisuride in de novo parkinsonian patients: a four-year follow-up. 329 46

Since the initiation of bromocriptine therapy for Parkinson's disease several newer dopamine agonists have been developed. Pergolide has reached the stage of Phase 3 clinical trials and will probably be available for general use sometime in the foreseeable future. Lisuride shows most promise in its parenteral form for infusion therapy of patients with severe fluctuations. Mesulergine, another ergot-derivative and ciladopa, a new non-ergot agonist, have been withdrawn from further clinical use due to tumorogenesis in rats. It is questionable how applicable these findings are to the use of the drugs in elderly humans with parkinsonism. Recently a small number of drugs have been found to have postsynaptic dopamine agonist properties only in the setting of denervated supersensitive dopamine receptors. These agents may be particularly effective in the early treatment of patients with Parkinson's disease. This paper will review a number of the dopamine agonists which have been developed since the introduction of bromocriptine therapy. Several of these have shown beneficial effects in early clinical trials while others show promise in preclinical studies of animal models of parkinsonism.
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PMID:Update on dopamine agonists in Parkinson's disease: "beyond bromocriptine". 331 48

Lisuride at a mean daily dose of 3 mg was given to 48 patients with idiopathic Parkinson's disease. Twenty received lisuride alone (Group A) and 36 received lisuride + L-Dopa + peripheral decarboxylase inhibitors (Group B). Dropouts were due primarily to lack of efficacy in Group A patients and to mental side effects in Group B patients. The patients who remained in the study for the full 4 years showed distinct improvement, which was maintained. Group A patients did not have the on-off phenomenon or abnormal involuntary movements.
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PMID:Lisuride in Parkinson's disease. 4-year follow-up. 340 56


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