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)

The antiparkinsonian activity of lergotrile mesylate, a presumed dopaminergic receptor stimulating agent, was investigating in monkeys with surgically induced tremor and in parkinsonian patients. The administration of lergotrile resulted in a dose-dependent reduction in the intensity of tremor in the monkeys. In 13 patients with Parkinson's disease treated with lergotrile (up to 12 mg a day), overall improvement was observed in five. Tremor was the main clinical feature to benefit, and the improvement reached statistical significance. In a subgroup of four patients treated with a higher dose of lergotrile (up to 20 mg a day), further improvement in rigidity and bradykinesia was noted, but again, only improvement in tremor was statistically significant. Adverse effects included orthostatic hypotension, behavioral alterations, and nausea and vomiting. These were severe enough to result in drug withdrawal in three patients.
 ...
PMID:Studies on the antiparkinsonism efficacy of lergotrile. 16 32

For many patients with Parkinson disease and levodopa-related motor fluctuations, the latency to onset of action of a single dose of a levodopa preparation may be both long and variable. In an effort to find a more rapidly acting and reliable preparation of levodopa, we therefore studied the efficacy of single doses of an oral solution of 250 mg of levodopa methyl ester (ME) with benserazide, 50 mg and of a molar equivalent dose of dispersible Madopar (DM) (50/200) in 13 patients in the fasting state after overnight drug withdrawal. The response of seven of these patients was compared to that after two Sinemet 25/100. The latency to "on" was equally fast with ME and DM, and significantly faster than after standard Sinemet. The duration of "on" was similar with all three. Because of this more rapid relief of "off" periods, both ME and DM offer a potential clinical advantage over standard preparations of levodopa.
 ...
PMID:The clinical efficacy of single morning doses of levodopa methyl ester: dispersible Madopar and Sinemet plus in Parkinson disease. 147 49

Deprenyl is a synthetic, selective inhibitor of the monoamine oxidase-B enzyme system. The mechanism of its beneficial effect in early and advanced Parkinson's disease is not settled. Increased striatal dopamine accumulation, sensitization of surviving dopamine neurons with increased dopamine production and reduced nigro-striatal toxicity may all contribute. The standard daily dose of deprenyl is 10 mg. Selectivity may be lost at higher doses. Deprenyl is especially indicated in untreated patients, improving up to 50 percent of patients with mild motor fluctuations. Major symptomatic benefit also occurs in occasional levodopa treated patients. Adverse effects are common, however. Increase dyskinesias, confusion and hallucinations, nausea and postural hypotension may necessitate drug withdrawal or the use of low dose regimens. Caution should be exercised with older patients, those with ulcer disease, which may be worsened by deprenyl, and individuals with active ischemic heart disease where the safety of this drug is not yet clear.
 ...
PMID:Deprenyl in Parkinson's disease: mechanisms, neuroprotective effect, indications and adverse effects. 157 60

CQA 206-291, a new D2 dopamine receptor agonist with a biphasic dopaminergic profile, was given to six patients with idiopathic Parkinson's disease after overnight drug withdrawal. With incremental single oral doses of CQA, a dose-related, clinically significant, and prolonged antiparkinsonian effect was observed. Most subjects experienced drowsiness after the drug while a minority of subjects experienced nausea and/or vomiting or postural hypotension. Further study of this drug in humans is indicated.
 ...
PMID:The antiparkinsonian activity of CQA 206-291, a new D2 dopamine receptor agonist. 256 66

The underlying cause of the long term complications of L-DOPA or dopamine agonist therapy in Parkinson's disease remains unknown. Previous studies of repeated administration of L-DOPA or bromocriptine to rodents have shown increases, decreases or no change in brain dopaminergic activity. For this reason we have re-examined the effects of chronic L-DOPA or dopamine agonist administration on brain dopamine receptor function in rats. Repeated intraperitoneal administration of L-DOPA to rats for 21 days followed by 3 days drug withdrawal caused an enhancement of apomorphine-induced stereotypy but no apparent alteration in striatal dopamine receptor numbers or affinity (as judged by 3H-spiperone; 3H-NPA and 3H-piflutixol binding). Chronic oral administration of L-DOPA plus carbidopa to rats for one year was without effect on apomorphine-induced stereotypy or striatal D-2 dopamine receptors. Similarly, no effects were observed on striatal dopamine function following one year's administration of bromocriptine. Pergolide produced an enhancement of apomorphine-induced stereotypy but a decrease in D-2 receptor density as judged by 3H-spiperone binding. In rats with a unilateral 6-OHDA lesion of the medial forebrain bundle the oral administration of L-DOPA plus carbidopa for 4 weeks, followed by 4 days withdrawal, enhanced the rate of apomorphine-induced contraversive rotation. It appears difficult, at least in rats, to manipulate striatal dopamine receptors with L-DOPA or dopamine agonist drugs. An enhancement of motor behaviour can occur in the presence of no change or a decrease in dopamine receptor numbers identified by in vitro ligand binding to tissue homogenates.
 ...
PMID:Receptor changes during chronic dopaminergic stimulation. 290 Feb 91

A 63-year-old woman with diagnosis of Parkinson's disease developed an unusual symptom complex which consisted of extrapyramidal symptoms, disturbances of consciousness, diaphoresis, fever, and increased serum creatine phosphokinase following the discontinuation of large doses of combined antiparkinsonian drugs. After the patient's condition did not improve with the first 14 days of treatment consisting of intravenous fluids and antibiotics, a trial administration of L-dopa and carbidopa brought about definite clinical improvement. The symptoms strongly resembled neuroleptic malignant syndrome which is often a serious complication of antipsychotic drugs. The symptoms and the treatment of the present case suggest that dopaminergic hypoactivity in the brain may be an important factor in antiparkinsonian drug withdrawal syndrome and that similar neurochemical mechanisms may exist in neuroleptic malignant syndrome.
 ...
PMID:Neuroleptic malignant syndrome-like state following a withdrawal of antiparkinsonian drugs. 611 84

Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson's disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood.
 ...
PMID:Blood to brain iron uptake in one rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol. 788 94

After overnight drug withdrawal and in the fasting state, 11 patients with Parkinson's disease (PD) and a fluctuating response to chronic levodopa treatment were given, in random sequence on consecutive days, equivalent levodopa doses (with peripheral decarboxylase inhibitor) (a) as levodopa methyl ester (ME), (b) as Sinemet CR, or (c) as half the dose of ME together with a halved tablet of Sinemet CR. All patients turned ON rapidly after treatments a and c, but only half did so after treatment b. On period duration was longest after treatment c, intermediate after treatment a, and shortest after treatment b. Pharmacokinetic analysis in a subset of 6 patients revealed no significant difference between treatments a and c, although there was a trend for t1/2 to be longer after treatment c. We conclude that giving ME with a halved tablet of Sinemet CR provided a useful clinical balance between rapid onset and extended duration of action of at least the first levodopa intake of the day. In view of differing release profiles between whole and halved tablets of Sinemet CR, similar single-dose pharmacokinetic studies, followed by sequential-dose clinical studies, are indicated when Sinemet CR 125 tablets soon become available.
 ...
PMID:Comparison between a fast and a slow release preparation of levodopa and a combination of the two: a clinical and pharmacokinetic study. 814 58

We characterized the clinical dose-response curves for relief of parkinsonism and production of dyskinesias as a function of plasma levodopa and 3-O-methyldopa levels in six patients with advanced Parkinson's disease (PD) and fluctuating responses to oral levodopa/carbidopa. Dose response to ramped intravenous levodopa infusion was measured after overnight drug withdrawal on two occasions: first after chronic, intermittent oral levodopa/carbidopa, and second after 3 to 5 days of continuous intravenous levodopa. Continuous intravenous levodopa shifted the dyskinesia dose-response curve to the right, reduced maximum dyskinesia activity, but did not significantly alter dose response for relief of parkinsonism. Improvement in dyskinesia was apparent by the second day of continuous levodopa, during which ratios of plasma dopa/3-O-methyldopa remained constant. Our results support the hypothesis that relief of parkinsonism and production of dyskinesia by levodopa occur by separate mechanisms.
 ...
PMID:Suppression of dyskinesias in advanced Parkinson's disease. I. Continuous intravenous levodopa shifts dose response for production of dyskinesias but not for relief of parkinsonism in patients with advanced Parkinson's disease. 820 27

In 1954, when he was five years old, a patient suffered from encephalitis with a prolonged lethargic state. Following this episode, he presented a severe parkinsonian syndrome which was associated, after a few years, with an axial dystonia and stereotyped involuntary movements of the upper limbs. These abnormal movements were particular by their coordinated appearance, their rhythmicity and their relative slowness. Treatment with L-dopa suppressed all akinetic, dystonic and dyskinetic symptoms. At age of 40 years, all the akinetic, dystonic and dyskinetic symptoms reappeared after drug withdrawal. Cerebral computed tomography, magnetic resonance imaging and fluorodeoxyglucose positron emission tomography were normal. Fluorodopa positron emission tomography revealed a significant bilateral reduction of tracer accumulation in the posterior part of both putamen, similar to that observed in patients with idiopathic Parkinson's disease. In this patient, pharmacological tests revealed that effectiveness of L-dopa was abolished by administration of a D2 antagonist, and was fully reproduced by a D2 agonist. Clinical signs, pharmacological data and past-medical history strongly suggested a limited lesion of the zona compacta of substantia nigra induced by viral agression. This complex and progressive extrapyramidal syndrome had strong similarities with the lethargic encephalitis of Von Economo and its late symptoms. Other diseases associating akinesia and dyskinesia or dystonic phenomena, like dopa-sensitive dystonia and juvenile Parkinson's disease, are very unlikely. Thus, the persistance of sporadic forms of Von Economo's encephalitis could be discussed.
 ...
PMID:[Parkinsonian syndrome and post-encephalitic stereotyped involuntary movements responsive to L-dopa]. 876 55


1 2 3 4 5 Next >>