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)

198 patients with Parkinson's disease on long-term treatment with L-dopa were evaluated for the presence of dyskinesias and psychiatric side-effects of the treatment. Dyskinesias were present in 53% of the patients. In a majority of them they appeared already during the first 2 years of the treatment. Younger patients seemed more susceptible to develop dyskinesias. Hallucinations, confusion, or delusions were observed in 22.2% of the patients. Older patients seemed more susceptible to develop these side-effects of the treatment. It seems that parkinsonian patients with later and earlier onset of the disease have different type of neuronal lesion responsible for the central side-effects of L-dopa.
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PMID:[Central side effects of long-term treatment of Parkinson disease with levodopa preparations]. 180 54

We reviewed the clinical and autonomic features of all patients with extrapyramidal and cerebellar disorders studied in the Mayo Autonomic Reflex Laboratory from 1983 to 1989. Patients were grouped into the following categories (number in parentheses): Parkinson's disease (35); parkinsonism-plus (54); multiple system atrophy (75); hereditary multisystem degenerations (eleven); progressive supranuclear palsy (32); non-familial cerebellar degeneration (eleven); nonspecific sporadic multisystem degeneration (73). Severe autonomic failure occurred in 97% of patients with multiple system atrophy and 53% of the nonspecific sporadic multisystem degeneration patients respectively. Autonomic involvement was mild or absent in Parkinson's disease while parkinsonism-plus and non-familial cerebellar degeneration patients had moderate autonomic failure. Orthostatic blood pressure reduction, percentage of anhidrosis on thermoregulatory sweat test, quantitative sudomotor axon reflex test, forearm response and heart rate response to deep breathing strongly regressed with severity. A response to levodopa treatment in patients with parkinsonism was more likely if cerebellar signs and cognitive deficits were absent. The presence of levodopa induced dyskinesia was also a marker for a clinically favourable levodopa response. We conclude that there is a spectrum of autonomic involvement in these degenerative disorders and that autonomic studies are useful in separating them and monitoring their course.
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PMID:Autonomic involvement in extrapyramidal and cerebellar disorders. 182 62

Sixteen parkinsonian patients, mean age 57 (range 41-71), with a mean 9 year duration of Parkinson's disease, with "on-off" motor fluctuations were treated with pergolide mesylate 1.6 mg/die (range 1-5) for three months. The treatment resulted in an improvement of akinesia, tremor and rigidity, of the severity of phase "off" and of the duration of time "on". No significant improvements were obtained in the severity of dyskinesia. Three patients considered the treatment excellent and capable of restoring their working abilities. The drug was generally well tolerated. Pergolide was discontinued because of orthostatic hypotension in two patients and because of hallucinations in one patient. We consider these results a favorable progress in the treatment of Parkinson's disease.
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PMID:[Pergolide mesylate in the treatment of Parkinson's disease resistant to other treatments. First Italian experience]. 182 72

A total of 240 patients of Parkinson's disease (PD) were studied (125 male, 115 female). The age of onset was 60.0 +/- 9.9 years(Y) (mean +/- S.D.) (range 30-87). A 0-4 rating score was applied on each of 6 major symptoms: i.e. tremor, rigidity, bradykinesia, gait, activities of daily living and fluctuation with maximum score of 24. According to the Hoehn and Yahr's stages, there were 44 cases in stage I, 141 in stage II, 31 in stage III, 19 in stage IV and 5 in stage V. Fluctuation in symptoms occurred in 42.9%, dyskinesia in 7.1%, psychosis in 9.6%, depression in 4.6%, and dementia in 2.9%. The mean duration of PD was 4.9 +/- 4.5 Y with 40% 5 years or longer. Significantly longer duration of PD was seen in the patients suffering from fluctuation (6.7 +/- 4.7 Y), dyskinesia (10.7 +/- 6.7 Y) and psychosis (9.4 +/- 6.5 Y). The mean duration of L-dopa treatment was 4.1 +/- 3.4 Y. The patients showing fluctuation (6.2 +/- 4.0 Y) or dyskinesia (7.6 +/- 4.7 Y) had significantly longer duration of L-dopa treatment. The mean daily dose of L-dopa was 370 +/- 203 mg. The patients with fluctuation (430 +/- 187 mg) or dyskinesia (545 +/- 265 mg) received significantly higher dose of L-dopa. Dementia tended to occur in the patients having later age of onset of PD (71.2 +/- 11.2 Y). The symptom score was significantly worse in those with fluctuation, dyskinesia, psychosis and dementia. It was well correlated with the Hoehn and Yahr's staging system.
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PMID:Abbreviated rating score for Parkinson's disease. 184 38

We studied the pharmacokinetics of levodopa and its metabolites in plasma and ventricular cerebrospinal fluid in 4 parkinsonian patients with indwelling Ommaya reservoirs placed at the time of previous adrenal-medullary to caudate nucleus transplantation. Cerebrospinal fluid levodopa levels were 11.9% of those in plasma. Motor performance and dyskinesia correlated more closely with the time course of the appearance of levodopa in the ventricular cerebrospinal fluid than with the plasma levodopa concentration and did not correlate with plasma 3-O-methyldopa or cerebrospinal fluid 3-O-methyldopa or homovanillic acid. Our data confirm that the wearing off of the levodopa effect in patients with advanced Parkinson's disease is a function of drug concentration in the central nervous system.
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PMID:Temporal relationships between plasma and cerebrospinal fluid pharmacokinetics of levodopa and clinical effect in Parkinson's disease. 154 43

Direct acting dopamine agonists are generally less effective than levodopa in relieving symptoms of Parkinson's disease. In an attempt to quantitate and explain this situation, the acute motor responses to intravenous injections of the dopamine agonist, (-)-N-n-propyl-norapomorphine hydrochloride (NPA), were compared with those of the dopamine precursor, levodopa. At optimum dose levels, the acute anti-Parkinsonian efficacy of NPA averaged only about 50% of maximum, while essentially total symptom suppression was obtained with levodopa in patients previously treated with the amine precursor. Dyskinesia severity, however, was similar with the two drugs. These differences in anti-Parkinsonian efficacy may reflect the fact that while NPA acts mainly on D-2 dopamine receptors, levodopa results in stimulation of both the D-1 and D-2 subsets of receptors at a more physiological ratio. Future efforts to develop dopamine agonists for the treatment of Parkinsonian symptoms may thus have to consider focusing on drugs having pharmacological profile more similar to that of dopamine.
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PMID:Comparison of the clinical pharmacology of (-)NPA and levodopa in Parkinson's disease. 186 1

Chronic administration of iminodipropionitrile (IDPN), a neurotoxin, to rats produces a persistent behavioral syndrome characterized by lateral and vertical head twitching, random circling and hyperactivity. Conventionally, this IDPN-induced dyskinesia has been considered to be due to abnormalities in the serotonin neuronal system. However, the present study also demonstrated marked alterations in the dopamine (DA) and acetylcholine (ACh) neuronal systems. These were activation of DA neurons in the nucleus accumbens and thalamus + midbrain, decreased activity in the other brain areas and a decrease in D1 DA receptors. ACh contents were decreased in most brain areas while muscarinic ACh receptors were increased in the striatum, superior colliculus and geniculate nucleus. These alterations in the ACh neuronal system may be secondary to abnormalities in the DA neuronal system. IDPN-induced dyskinesia was enhanced by administration of L-dopa, which increases DA concentration, but was completely inhibited by ceruletide, which inhibits DA release. The dyskinesia was also inhibited by sulpiride, a central antagonist of D2 DA receptors. Interestingly, apomorphine and bromocriptine, which are DA receptor agonists, did not aggravate, but decreased dyskinesia in the IDPN-treated rats. These results strongly suggest that dyskinesia is caused not by abnormality of postsynaptic receptors in the DA neuronal system but by abnormally enhanced function of the presynaptic DA neurons themselves. In addition, ceruletide may be useful in the treatment of dyskinesia, and bromocriptine alone or in combination with L-dopa may be effective in Parkinson's disease without the development of dyskinesia. Thus, the IDPN-treated rat model is useful for clarifying the biochemical pathophysiology of dyskinesia and developing drugs for its treatment.
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PMID:Neurotransmitter and receptor alterations in the rat persistent dyskinesia model induced by iminodipropionitrile. 196 33

Long-term treatment of human Parkinson's disease with levodopa or dopamine agonists is often complicated by the appearance of abnormal involuntary movements (dyskinesias) that are extremely difficult to control. Little is known of the cause, pathophysiological mechanisms, or possible strategies for amelioration of this manifestation of dyskinesia. A hypothesis is set forth on the neural mechanisms that mediate levodopa- or dopamine agonist-induced dyskinesia (in particular chorea) as a side effect of the treatment of parkinsonism. Evidence is drawn from both clinical observations and experimental studies in a spectrum of movement disorders ranging from ballism through chorea to parkinsonism. It is proposed that (a) All forms of chorea, whatever their origin, share a common underlying neural mechanism. (b) Disordered activity of the subthalamic nucleus is central to the generation of choreic movements. In levodopa- or dopamine agonist-induced dyskinesia, (c) The site of action of dopaminergic agents in causing chorea is the putamen. (d) The specific pathophysiological state conducive to the appearance of chorea is brought about by the long-term exposure of the dopamine-depleted (parkinsonian) putamen to exogenous dopaminergic agents. (e) Long-term exposure to dopaminergic agents causes (either directly or indirectly) preferential inhibition of the subpopulation of putaminal neurones that project specifically to the lateral segment of the globus pallidus. This causes disinhibition of lateral pallidal neurones, which become overactive and physiologically inhibit the subthalamic nucleus. (f) The hypothesis suggests a number of possible strategies that might be useful for the alleviation of levodopa-induced dyskinesia.
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PMID:A hypothesis on the pathophysiological mechanisms that underlie levodopa- or dopamine agonist-induced dyskinesia in Parkinson's disease: implications for future strategies in treatment. 197 Jan 20

Many drugs may cause extrapyramidal disturbances which in most instances are due to interference with cerebral dopaminergic mechanisms. Neuroleptics are prominent in this group of drugs. Drug-induced Parkinson's syndrome, acute dystonia, late-onset dyskinesia and the malignant neuroleptic syndrome are discussed.
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PMID:[Iatrogenic extrapyramidal disorders]. 197 12

Ten patients with Parkinson's disease (PD) with motor fluctuations that responded to a protein redistribution diet were studied. All 10 patients were receiving standard Sinemet (levodopa/carbidopa). Five randomly selected patients were changed from standard Sinemet to a controlled-release form of Sinemet. The other five patients continued to receive standard Sinemet. To maintain the same degree of control of PD in the five patients switched to the controlled-release form of Sinemet, the daily levodopa intake increased. While receiving optimal therapy (standard Sinemet or controlled-release Sinemet) and a protein redistribution diet, all 10 patients then underwent hourly videotaping and blood sampling (for plasma levodopa levels) during 2 consecutive days. Videotapes were blindly reviewed for PD disability, dyskinesia, and the time required to walk a measured distance. Comparing the two groups, standard Sinemet with controlled-release Sinemet, respectively, mean levodopa requirements were 505 and 1895 mg, plasma levodopa levels were 6.1 and 17.6 mumol/L, and abnormal involuntary movement scale scores were 14 and 26. Their mean PD disability scores did not differ statistically or clinically. Also no statistically significant differences were noted in either their mean walking times or their mean daily dose frequencies.
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PMID:Standard and controlled-release levodopa/carbidopa in patients with fluctuating Parkinson's disease on a protein redistribution diet. A preliminary report. 201 14


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