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)

Two prospective projects were started in May 1985 to evaluate the long-term effects of bromocriptine in patients with Parkinson's disease. One of the projects is to see if combination therapy with levodopa and bromocriptine is superior to levodopa alone with regard to the prevention of late side effects of levodopa therapy. The other is to see the long-term effects of bromocriptine monotherapy. Patients with Parkinson's disease were allocated randomly to either combination or levodopa group in the first project. Parkinsonian symptoms, disabilities of daily life and severity of late side effects of long-term levodopa therapy were evaluated by a semiquantitative rating scale. This communication represents the first interim report. Methods of the studies and synopsis of the results at the end of the 12th month are described. A total of 702 patients was enrolled in the study (combination therapy, n = 216; levodopa therapy, n = 200, bromocriptine monotherapy, n = 286). At the end of the 12th month, the numbers of patients who dropped out from the study were 19, 16 and 55 in the three groups, respectively. It appears to be too early to make any definite conclusion with regard to which mode of treatment is superior, however, some evidence suggesting a superiority of the combination therapy over levodopa alone was noted in managing wearing-off phenomenon and dyskinesia. As many patients are sticking to the originally intended mode of treatment, it appears to be possible to obtain more meaningful data in several years.
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PMID:A nation-wide collaborative study on the long-term effects of bromocriptine in patients with Parkinson's disease. First interim report in Japan. 337 60

A retrospective study of the treatment of 148 patients with severe parkinsonism is reported. After dopa preparation was introduced as a treatment for Parkinson's disease the progress of the disease has changed. More patients with first signs after 1970 had mild progression of disease compared to patients with a debut before 1970. In addition, the population with manifestations after 1970 had fewer cases of severe progression. Adverse effects of dopa treatment had been observed in 70% of the patients. After 5 years of treatment with dopa preparation, 62.1% of the patients had momentary peak-dose dyskinesia. After 2 years of treatment 14.2% of the patients had on-off effects with higher incidence after further treatment. One hundred and fifteen patients have been treated with bromocriptine, 27 patients for more than 5 years.
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PMID:Outpatient treatment of Parkinson's disease. 338 13

We compared 46 patients having onset of Parkinson's disease before age 45 years with 52 having onset after age 70. Young-onset cases more often presented with muscular stiffness (43%) and old-onset with difficulty walking (33%). One-third of young-onset cases had off-period dystonia, mostly affecting the legs, but no dystonia was recorded in old-onset cases. Presentation with rest tremor occurred in 41% of young-onset and 63% of old-onset. There were no differences in the number of affected relatives, endocrine disease, personality characteristics, dementia, or dyskinesia. A pathological study of 12 young-onset and 22 old-onset cases showed 24% greater nigral cell loss in the young, but no differences in the basic Lewy body pathology. Median disease duration in young cases was 5 years longer in the clinical study and 12 years longer in the pathological study. These studies show that the Parkinson's disease process is similar in young- and old-onset cases.
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PMID:A comparison of clinical and pathological features of young- and old-onset Parkinson's disease. 341 87

The effect of repeated administration of bromocriptine and L-3,4-dihydroxyphenylalanine (L-DOPA) was studied behaviorally and biochemically in rats with a unilateral lesion of the nigrostriatal pathway. Groups of rats injected eight times with bromocriptine or L-DOPA significantly increased their contraversive circling. Rats receiving only two injections of bromocriptine did not. Animals receiving two injections of L-DOPA showed a slight but significant increase in circling. The affinity of the binding of [3H]spiperone to the dopamine receptors was unchanged by the lesion or the treatments, while the density of the binding was significantly modified. Chronic treatment with bromocriptine induced a significant decrease in the density of D2 dopamine receptors in the intact striata, while on the lesioned side, it remained unchanged. By contrast, chronic administration of L-DOPA induced a significant increase in density of the striatal dopamine receptors in the lesioned striata in addition to that caused by denervation, while the decrease on the intact side was not significant. It seems that contrary to the intact striatum, the lesioned side had a defective down-regulation mechanism in response to chronic treatment with a dopamine agonist. The results also show that L-DOPA was more potent than bromocriptine in inducing agonist supersensitivity in a denervated striatum. This may explain why chronic treatment with bromocriptine has a lesser tendency to induce dyskinesia in patients with Parkinson's disease.
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PMID:Behavioral and biochemical evidence for a different effect of repeated administration of L-dopa and bromocriptine on denervated versus non-denervated striatal dopamine receptors. 343 63

Low-dose bromocriptine therapy and low-dose levodopa-carbidopa therapy are being compared in a double-blind study over a five-year period as treatment for newly-diagnosed patients with Parkinson's disease. Ninety-four patients had entered the study by January 1986 and of these, 50 had been followed for six months or more. Preliminary results confirm that many patients with Parkinson's disease can be managed satisfactorily in the early stages of the disease with low-dose therapy. Three patients, all of whom were receiving levodopa-carbidopa therapy, developed dyskinesia. Twelve patients who had received bromocriptine had an inadequate response or developed confusion or postural hypotension. Of these patients, six had a poor response to subsequent levodopa-carbidopa therapy. While the initial improvement that results from low-dose bromocriptine therapy and low-dose levodopa-carbidopa therapy is less than one would expect with conventional doses of these agents, it is hoped that this approach will reduce the incidence of long-term side-effects such as dyskinesia and fluctuations.
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PMID:The Sydney multicentre study of Parkinson's disease. The first 18 months. 355 78

Tremor and drug-induced dyskinesia are major involuntary movements in Parkinson's disease. The rhythm of resting tremor is 4-6 cycles/s, driven by generators in the brain, and stabilized by reflex arcs involving the spinal cord, nerves and muscles. Its frequency is fixed: it is the same in proximal and distal muscles in each case and does not change in the course of amplitude reduction of tremor by levodopa injection. An approximate doubling of frequency occurs in action tremor which suggests a central mechanism liable to produce harmonics. In postural tremor as observed in the lower limbs while on standing, the frequency of grouped discharges falls into ranges of rhythm with either resting or action tremor. Levodopa-induced dyskinesia has a similar nature to chorea in both clinical observation and EMG. With EMG choreic discharges may appear concomitant with regular parkinsonian tremors in the same muscle, suggesting that the two are not opposites as expressions of dysfunction of the dopaminergic system.
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PMID:Pathophysiology of involuntary movements in Parkinson's disease. 355 88

Ciladopa is a partial dopamine agonist that is effective in patients with advanced Parkinson's disease who are no longer satisfactorily responding to levodopa. Thirty-one patients participated in a double-blind randomized study of ciladopa (added to levodopa) versus placebo. Among 21 patients randomized to treatment with ciladopa and levodopa, there was a 32% decrease in symptoms on the Modified Columbia University Disability Scale. This change was significant, p less than or equal to 0.05. Eight of the 21 patients (38%) improved by at least 50%. The mean number of hours "on" increased by 20%. This change was significant, p less than or equal to 0.05. Five of the 21 patients (24%) were on for at least 4 hours more than at baseline. Dyskinesias were not increased. The mean dose of ciladopa was 19.5 mg/d. The mean dose of levodopa in Sinemet was decreased by 10%. Studies with ciladopa in humans had to be discontinued because of the occurrence of microscopic testicular tumors in some rodents. Although improvement in patients taking ciladopa was modest, there were few adverse effects. These results are encouraging, because two other partial agonists are now available, and they may be as effective as ciladopa.
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PMID:Advanced Parkinson's disease: use of partial dopamine agonist, ciladopa. 357 92

As the direct agonist with the widest clinical use, bromocriptine provides a unique window into the clinical spectrum of Parkinson's disease. The efficacy of bromocriptine for therapy of de novo Parkinson's disease has recently been confirmed using a double-blind design with L-Dopa (Sinemet). Over a period of 5.5 months, bromocriptine was found to be as effective as L-Dopa in reducing the functional and neurological disability of Parkinson's disease. This study complements others and demonstrates a role for bromocriptine as de novo therapy. A longitudinal study comparing bromocriptine with L-Dopa is underway, but previous observations with bromocriptine suggest modest, transient beneficial effects with significantly less fluctuation of disability and less dyskinesia when used alone or in combination with L-Dopa. The transient benefits of bromocriptine on progressive disability suggest that both pre- and post-synaptic defects are eventually involved in Parkinson's disease. While agonists with improved efficacy and minimal side effects are required for symptomatic treatment of Parkinson's disease, strategies to protect pre- and post-synaptic neuron populations against progressive dysfunction must be developed.
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PMID:Bromocriptine and the clinical spectrum of Parkinson's disease. 367 20

This paper presents a review of the literature on the therapeutic action and the side effects of the two main dopaminergic agents: L-DOPA/decarboxylase inhibitor (L-DOPA/DI) and bromocriptine (Parlodel used either as monotherapy or in combination in patients with Parkinson's disease. The combination of L-DOPA/DI and bromocriptine gives the best therapeutic efficacy (49% improvement) in the total score (bradykinesia, rigidity and tremor). However, treatment by monotherapy or combination gives the same pattern of activity: greatest improvement in tremor, followed by rigidity and bradykinesia. Improvement observed in the short term is not sustained over longer periods of time for monotherapy with either drug. The short-term side effects are similar for each treatment, whereas long-term complications (dyskinesia, end-of-dose deterioration and on-off phenomenon) appear only when levodopa is used, alone (high incidence) or in combination with bromocriptine (low incidence). The overall optimum treatment is obtained with a combination of L-DOPA/DI and bromocriptine.
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PMID:Optimum symptomatic control of Parkinson's disease with dopaminergic therapy. 367 21

We report two patients with dyskinesia responding to antidepressants. The first is a 70-year-old man with depression, Parkinsonism and neuroleptic-induced tardive dyskinesia who presented with hysterical mutism. After recovery from the mutism, he was started on desipramine for depression. One week later the dyskinesia improved markedly. The second patient is a 61-year-old man with Parkinson's disease, dementia, depression and L-dopa-induced oro-lingual-facial dyskinesias. He was taking levodopa, trihexyphenydil and bromocriptine. The depression was treated first with desipramine and later with trazodone. The dyskinesia improved significantly on both drugs. The response of the dyskinesias to antidepressant medication may be due to the fact that antidepressants decrease beta-adrenoreceptor sensitivity and density which in turn may result in a diminished release of dopamine since beta-adrenoceptors mediate the noradrenaline-stimulated release of dopamine.
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PMID:Response of tardive and L-dopa-induced dyskinesias to antidepressants. 369 Apr 36


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