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)

MPTP induces parkinsonism in monkeys by destruction of the substantia nigra, pars compacta. It can also damage ventral tegmental dopamine neurones and the noradrenergic locus coeruleus, both of which may be affected in Parkinson's disease. Motor symptoms in MPTP-treated monkeys respond readily to levodopa or dopamine agonist therapy. Administration of levodopa over 4-8 weeks leads to the emergence of "peak-dose" dyskinesia. Such abnormal movements are not seen following challenge doses of levodopa in animals not on long-term therapy. Radioligand studies reveal a 40-180% increase in D2 receptor binding in the striatum of parkinsonian monkeys. 2-deoxyglucose studies of regional brain metabolism indicate that MPTP-induced parkinsonism is characterised by abnormally increased activity of medial pallidal neurones which project to the thalamus and pedunculopontine nucleus and reduced activity of subthalamic nucleus neurones.
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PMID:MPTP-induced parkinsonism in the monkey: neurochemical pathology, complications of treatment and pathophysiological mechanisms. 311 80

Pergolide is thought to stimulate both D1 and D2 dopaminergic receptors. Its effects on Parkinson's disease were evaluated in an open trial, using clinical assessment scales and objective tests. Nine patients had previously been treated with L-dopa, but the drug had either gradually lost its effectiveness or produced invalidating side-effects. Pergolide in doses of 2 mg per day considerably and durably improved the parkinsonian symptoms and enabled the patients to reduce L-dopa dosage by about 50%. Dyskinesia and "on-off" phenomena partially regressed. Significant improvement was also observed in 3 of 4 patients with Parkinson's disease who had not previously received L-dopa. The side-effects of pergolide were fairly frequent in both groups, but they were relatively mild and reversible.
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PMID:[Clinical study of pergolide in Parkinson's disease]. 316 Oct 45

The experience that the supplementation of depleted dopamine in the nigro-striatal system of parkinsonian patients with L-dopa improves the clinical triad, akinesia, rigidity and tremor, mainly applies to long-term treatment in the early phase of Parkinson's disease. Complications in motor performance, like on-off response, wearing-off phenomena, peak-dose dyskinesia, biphasic dyskinesia, off-period dystonia and others, after more than 3 to 5 years following the onset of treatment indicate fluctuations in the dopaminergic feedback control system. It is suggested that these complications are due to progressive presynaptic degeneration and late changes in postsynaptic receptor amplification. However, as fluctuations are not imperative in all patients, an important additional aspect seems to be the topography of denervation, which involves different portions of the striatum to varying degrees. Location and extent of denervation are criteria which appear to have predictive value for the malignancy of the disease, the therapeutic response of drugs and complications in long-term treatment.
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PMID:Factors contributing to fluctuations of the dopaminergic nigro-striatal feedback system in Parkinson's disease. 316 34

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

The contribution of central pharmacodynamic mechanisms to the pathogenesis of motor fluctuations in advanced Parkinson's disease was studied in 29 patients by evaluating their acute response to intravenously injected levodopa. While the threshold dose for an antiparkinsonian effect did not change, that for induction of dyskinesia showed a progressive reduction in 4 groups: (1) levodopa-naive patients, (2) those with a stable response to oral administration, and (3) those with wearing-off or (4) on-off fluctuations. Concomitantly, the therapeutic window for levodopa narrowed and the levodopa dose-antiparkinsonian response slope increased. The antiparkinsonian threshold dose correlated best with duration of symptoms; the dyskinesia threshold dose, therapeutic window, and dose-response slope related most closely with the duration of levodopa treatment. The differing dose-response profiles for the antiparkinsonian and dyskinetic effects suggest involvement of separate pharmacological mechanisms. The present results, taken together with previous observations that the wearing-off phenomenon responds promptly to plasma levodopa stabilization while on-off fluctuations tend to diminish over several days, suggest that postsynaptic modifications, presumably at the receptor level, serve as the major determinant for the increasing difficulty with optimal dose adjustment and the motor fluctuations, especially of the on-off type, which complicate levodopa therapy of patients with advanced Parkinson's disease.
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PMID:Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, Part II. 322 71

Dementia and extrapyramidal signs combine in both Alzheimer's disease (AD) and Parkinson's disease (PD) to produce various degrees of clinical overlap between the two diseases. Rest tremor, positive motor response to dopaminergic drugs, bradyphrenia and disproportionate deficits in visuospatial function, dating capacity, recency discrimination, sequencing and set-shifting are specific features of PD; myoclonus, orofacial dyskinesia, aphasia and rapidly progressive global dementia favours AD. A clearer analysis of the underlying brain-behaviour relationships is necessary to advance our understanding of the origin of cognitive and motor impairment and its treatment.
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PMID:Clinical similarities and differences between Alzheimer's disease and Parkinson's disease. 331 3

Results obtained in 22 patients with Parkinson's disease in whom treatment with standard Madopar was replaced by Madopar HBS, a CR formulation of the same product, are presented. All the patients presented with dyskinesia and akinesia phenomena related in part to the L-dopa treatment and in part to the disease itself. In 20 patients replacement of the standard agent by HBS led to a distinct improvement in the clinical condition and a significant reduction of the 'on-off' phenomenon. However, with the new formulation the dosage had to be increased by 86% on average as compared with standard Madopar. In 6 of the 22 patients treatment with the HBS formulation has continued for over 6 months and is still giving very good results.
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PMID:Treatment of parkinsonian conditions with a controlled-release form of levodopa--preliminary study. 332 39

In 23 patients with idiopathic Parkinson's disease presenting with severe fluctuations in motor performance and 'on-off' phenomena after long-term treatment with levodopa, the standard form of Madopar was replaced by the controlled-release form Madopar HBS. The Meerwaldt's patient card has been used to evaluate the frequency and intensity of response swings. Only 2 patients, who suffered from clear-cut 'end-of-dose' deterioration, significantly benefited by this switch from standard Madopar to Madopar HBS. Eight patients had a minimal or not essential improvement of the parkinsonian symptomatology and/or of the response fluctuations. Thirteen patients returned to their previous standard Madopar treatment after deterioration of parkinsonian symptoms or increase of dyskinesia under the HBS treatment. The overall increase in dosage of levodopa with Madopar HBS was 54% in comparison with the initial standard Madopar dosage.
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PMID:Open multicenter trial with Madopar HBS in parkinsonian patients. Preliminary assessment after short-term treatment. 332 41

Long-term observation over 3-8 postoperative years of cases of Parkinson disease operated by stereotactic thalamotomy using a microelectrode recording technique is reported. The procedure is specifically useful in the following four groups: (1) tremor-dominant cases, (2) hemiparkinsonism, (3) cases with marked asymmetry in motor symptoms and (4) juvenile parkinsonism presenting levodopa-induced dyskinesia.
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PMID:Long-term follow-up study of nucleus ventralis intermedius and ventrolateralis thalamotomy using a microelectrode technique in parkinsonism. 332 71

Madopar Hydrodynamically Balanced System (HBS), a new sustained-release levodopa preparation, was used to control severe nightly disabilities in 15 outpatients suffering from Parkinson's disease in an advanced state and with long-term levodopa therapy. This medication was given ante noctem in addition to an otherwise unchanged daily regimen of levodopa administration. In 13 patients a considerable diminution in nocturnal akinesia and in the frequency of waking up was reached with a mean dosage of 308 mg of Madopar HBS. Early morning akinesia was only slightly alleviated in four patients. The nocturnal off-period pain disappeared in one patient. Adverse effects consisted of nocturnal dyskinesia in two patients and early morning dystonia in another two patients. The regular use of sleeping pills was clearly reduced after Madopar HBS therapy.
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PMID:Madopar HBS in Parkinson patients with nocturnal akinesia. 335 32


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