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)

The effect of a new dopaminergic agonist, piribedil, was studied in 16 patients with Parkinson's disease and compared with placebo and L-DOPA. Piribedil appeared to have a moderate therapeutic effect that was significantly less than that of L-DOPA. Tremor appeared to be the main clinical feature to benefit. Nausea, vomiting, and somnolence were most frequent during the buildup of treatment and confusion and hallucinations during long-term treatment. Piribedil caused a significant decrease in probenecid-induced accumulation of HVA in the CSF, suggesting reduced turnover of endogenous dopamine in the brain. There was a significant relationship between dopamine receptor activation by piribedil and improvement of parkinsonian disability.
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PMID:Dopaminergic agonist effects on Parkinsonian clinical features and brain monamine metabolism. 109 75

The further therapeutic benefit of piribedil when combined with amantadine or Levodopa was studied by a double-blind, cross-over trial in 15 patients with Parkinson's disease. A significant improvement at the 5 per cent level for akinesia, gait, speech disorder and facial expression occurred when piribedil was added to Levodopa; and a more highly significant improvement at the 1 per cent level for akinesia, facial expression and finger dexterity occurred with piribedil and amantadine. No significant improvement occurred for special timed tests. Improvement was associated with side effects in both groups of patients. Side effects occurred with both placebo and active piribedil. Only nausea during piribedil and Levodopa treatment reached statistical significance when compared with the placebo. Piribedil did not give rise to any haematological or biochemical complications. Our findings suggest that piribedil is of further therapeutic benefit when added to amantadine or Levodopa. It was suggested that the improvement which occurred together with amantadine could be due to the combined action of both drugs on dopamine receptors.
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PMID:Piribedil (ET 495) in the treatment of Parkinson's disease combined with amantadine or levodopa. 109 59

The recording technique described makes possible the detailed analysis of hypertonia and tremor in Parkinson's disease, as well as the action of different drugs. It may contribute to the understanding of the physiopathological basis of these motor disturbances and the mode of action of anti-parkinsonian drugs. It also represents a reliable method of repeated observation, independent of subjective factors, in the evaluation of the long-term effectiveness of a medication. We were particularly concerned with the evaluation and comparison of the effect of different drugs in the course of a short study, involving the administration of a single dose of the medications used. In this way were studied: Apomorphine, given sub-cutaneously in non-emetic doses, which decreases in a constant and spectacular fashion both tremor and hypertonia ; Piribedil (1-3 mg IV) ; L-Dopa (100 mg IV) ; Ro-080576/007 F in a dose of one capsule containing 200 mg of L-Dopa and 50 mg of L-dopa-decarboxylase inhibitor. The effect of these various medications was invariable greater than that of a placebo and lasted much longer. With these doses, and under the special experimental conditions of this study, Piribedil was better tolerated and in general more active than L-dopa, in particular in relation to tremor. The action observed in the course of this short study prior to treatment might, to a certain extent, make it possible to predict the effect of long-term treatment.
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PMID:[Polygraphic recording of tremor and of hypertonic phenomena. Application to the action of various drugs]. 110 46

Interaction between dopamine and phospholipids was studied in the substantia nigra of ten patients with Parkinson disease and nine control subjects. There were no differences in the total content of phospholipids. However, in parkinsonian patients without previous levodopa treatment, the amount of sphingomyelin was increased and the amount of phosphatidylethanolamine and phosphatidylcholine decreased. Levodopa treatment corrected these values to the level of controls, whereas the amount of phosphatidylserine was decreased. It is concluded that changes in phospholipids are reflections of the deficiency of dopamine and loss of dopaminergic neurons in the substantia nigra of patients with Parkinson disease.
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PMID:Interaction between dopamine and phospholipids. Studies of the substantia nigra in Parkinson disease patients. 111 56

One of the major difficulties in the treatment of Parkinson's disease with L-Dopa alone or associated with a decarboxylase inhibitor lies in the frequent occurrence of involuntary movements. In some cases these movements can be prevented (eliminated) by increasing the plasma DCI concentration or by associating 3-oxy-methyl-dopa. In resistant cases the authors have conducted a trial with EP 19-088, which belongs to a new class of tricyclic derivatives of indenopyridine. The trial population comprised 42 patients. In 12 of these there was complete cessation of symptoms. In 9 patients a marked improvement was noted, while in 10 others the improvement was slight but definite. The treatment was discontinued in 2 cases due to episodes of increased confusion. In the other 9 patients the experimental treatment had no effect. No side effects were observed in 24 of the 42 patients tested. In addition to symptoms such as nausea or transient heartburn, the remaining patients reported either a slight worsening of their parkinsonian symptoms or an increase in diurnal fatigability.
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PMID:[Abnormal movements induced by L-dopa. New therapeutic possibilities]. 112 79

To estimate the effect of long-term administration of L-3,4-dihydroxyphenylalanine (L-Dopa) on methylation of compounds not formed from it, the urinary excretion of histamine and its methylated metabolites was studied in rats and guinea pigs fed L-Dopa in their diets and in patients with Parkinson's disease being treated with L-Dopa. In the guinea pigs, but not in the rats, L-Dopa administration decreases excretion of histamine and of its methylated metabolites, methylhistamine and 1-methylimidazole-4-acetic acid. Because excretion of 1-methylimidazole-5-acetic acid, which comes from the diet and is not a metabolite of histamine, was unaffected by the L-Dopa treatment, the decreases were due to a specific effect of L-Dopa on histamine metabolism. When compared to normal control subjects, patients with Parkinson's disease excreted less histamine and methylhistamine, both before and during treatment with L-Dopa. Administration of the peripheral aromatic L-amino acid decarboxylase inhibitor, L-alpha-methyldopa hydrazine (MK 486), decreased urinary excretion of histamine markedly. Neither L-Dopa nor MK 486 appeared to influence excretion of the imidazoleacetic acids in the patients. The results suggest that L-Dopa may decrease histamine formation or release in some species but that it does not influence histamine methylation.
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PMID:Effect of L-DOPA on endogenous histamine metabolism. 115 52

Levodopa-induced dyskinesias frequently limit the clinical efficacy of levodopa therapy in Parkinson's disease. Deanol recently has been reported to be of value in relieving the dyskinesias by acting through a central cholinergic mechanism. Seventeen outpatients with levodopa-induced dyskinesias were given deanol in dosages of 300 to 900 mg per day. The dyskinesias improved in four of the patients, remained unchanged in five, and worsened in eight. In all four patients who showed improvement after institution of deanol therapy, the improvement continued after the patients were switched to a placebo. One of these patients also demonstrated improvement in his parkinsonism, while two others experienced a worsening in their parkinsonism. Deanol does not appear to be effective in the treatment of levodopa-induced dyskinesias.
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PMID:Deanol in the treatment of levodopa-induced dyskinesias. 116 39

Metoclopramide antagonises apomorphine-induced stereotypy in rats (ED50 1.5 mg/kg), apomorphine reversal of reserpine-induced locomotor suppression in mice (50% inhibition produced by 17 mg/kg), and apomorphine- or amphetamine-induced turning behaviour in mice with unilateral lesions of the striatal dopaminergic nerve terminals (ED505.0 and 4.0 mg/kg respectively). Metoclopramide resembles pimozide in all these respects and appears to be a relatively potent antagonist of striatal dopamine receptors. Yet metoclopramide, in anti-emetic doses, has no effect on disability in Parkinson's disease or on the therapeutic benefit of L-Dopa and L-Dopa dyskinesias.
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PMID:Pharmacological evidence for cerebral dopamine receptor blockade by metoclopramide in rodents. 117 87

A group of 71 patients with Parkinson's disease were treated with L-Dopa and benserazide during periods ranging from 27 to 60 months. In 28% of cases a decline in therapeutic effects and or delayed appearance or increase of secondary actions were observed constituting a long-term syndrome. Its most complex and dramatic expression, the on-off effect, was present in 11% of cases. Those patients with more severe symptoms were studied by means of continuous clinical observation enabling the design of daytime follow-up curves. Observations were repeated with varying dosage patterns, showing variations but no substantial changes or disappearance of the symptoms described. Electromyographic recordings and films were taken in certain cases defining the characteristics of on and off effects. Several procedures were implemented in an attempt to control Long-Term Syndrome manifestations: Change of dosage, variation of L-dopa/decarboxilase inhibitor ratio, association of anticholinergic agents with antidepressants, hypoprotein diets. Improvement was moderate and/or transient, with the exception of Nortriptilline which permitted total or partial control of certain symptoms, especially hypokinetic periods, bouts of tremor and dystonic attitudes. It was occasionally necessary to interrupt administration of L-Dopa, readministering it later with recovery of the therapeutic effect and/or avoidance of undesirable effects for varying periods of time. Loss than optimal doses proved beneficial in reducing or postponing Long-Term Syndrome manifestations. Although L-Dopa does not detain the course of the disease, the persistence of favourable results in most patients for prolonged periods of treatment confirms the long-term therapeutic value of this drug.
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PMID:[Long-term syndrome in the treatment of parkinsonism with L-dopa]. 124 97

It is now generally acknowledged that L-Dopa is the therapy of choice for Parkinson's Disease. However, L-Dopa has some short comings: It requires large daily dosage, the therapeutic benefits are achieved only after a delayed onset of 1-2 months, and it has a number of side effects both central and peripheral. In the last few years there has been an intense search for agents that are less toxic, more efficient and more rapidly acting that L-Dopa. The ideal agent has not yet been found. However, a combination therapy with L-Dopa and dopa decarboxylase inhibitors has shown promise. The decarboxylase inhibitors used have a large molecule which does not cross the blood brain barrier. Thus when L-Dopa and the decarboxylase inhibitor are given togehher, peripheral production of dopamine from L-Dopa is inhibited, therefore, rendering L-Dopa more readily and rapidly available for brain metabolism. In the present paper we present the results of the treatment of 50 patients on combined therapy using L-Dopa combined with Carbidopa.
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PMID:L-dopa-carbidopa: combined therapy for the treatment of Parkinson's disease. 125 61


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