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)

Post-mortem brain material from control and Parkinson's disease patients was examined to elucidate further the neurochemistry of this disease and to determine the mechanism of action of L-dopa as a therapeutic agent. The activities of L-aromatic amino acid decarboxylase (dopa D), tyrosine hydroxylase, monoamine oxidase and catechol-O-methyl transferase were examined; in addition the tissue levels of dopa, 3-O-methyldopa, dopamine (DA) and homovanillic acid (HVA) were determined. In the non-dopa-treated Parkinsonian patients, the greatest decreases were detected for striatal DA and dopa D, with homovanillic acid and tyrosine hydroxylase levels showing a lesser change. The activities of monoamine oxidase and catechol-O-methyl transferase in the striatal nuclei were not different from the controls. The putamen was consistently the most severely affected region. Dopa and 3-O-methyldopa were detectable in all brain areas only in those patients treated with L-dopa shortly before death. The mean concentrations of DA in the striatum of these patients were 1) 9 to 15 times higher than those in non-dopa-treated patients, 2) related to the time before death of the last dose of L-dopa and 3) greater in the striatum of patients clinically classified as "good responders" as compared to "poor responders." Although L-dopa therapy increased homovanillic acid levels in all brain areas, a preferential increase was observed in the striatum. It was concluded that L-dopa's principal therapeutic effects in Parkinson's disease are consistent with its transformation to DA in the striatum.
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PMID:The neurochemistry of Parkinson's disease: effect of L-dopa therapy. 0 Apr 89

In an attempt to determine the mechanism of action of L-proly-L-leucyl-glycine amide (MIF-I) in the treatment of Parkinson's disease, various parameters of dopaminergic neuronal function were studied in rats. It was found that the active uptake of 3H-dopamine (3H-DA) by synaptosome-rich homogenates of the striatum of rats treated with MIF-I (1 mg/kg IP X 3, 24 hr intervals) was unaltered 1 hr after final treatment with MIF-I. Also, neither tyrosine hydroxylase nor dopa decarboxylase activity was altered in the striatum and substantia nigra of rats treated with MIF-I (20 mg/kg IP X 3, 24 hr intervals). Thus, vital functional processes associated with dopaminergic neurons apparently are not altered by MIF-I under the conditions studied. These findings illustrate the importance of concurrent DOPA administration in observing an effect of MIF-I on dopaminergic neuronal function.
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PMID:Effects of L-prolyl-L-leucyl-glycine amide (MIF-I) on dopaminergic neurons. 1 12

The pathophysiology, anticholinergic therapy and dopaminergic therapy of Parkinson's disease are reviewed; an emphasis is placed on the structure and function of the basal ganglia because of their importance in understanding the pharmacotherapy of parkinsonism. The pharmacologic management of Parkinson's disease is limited primarily to manipulation of the dopamine-acetylcholine system. Levodopa, with or without a peripheral dopa decarboxylase inhibitor, is the current drug of choice in the management of idiopathic and postencephalitic Parkinson's disease. Modification of the serotonin-histamine system via the use of antihistamines may be useful in some patients. There are also many adjunctive agents which may be employed in combination with or in place of levodopa. Levodopa clearly has no place in the treatment of neuroleptic-induced Parkinson's disease; anticholinergics and antihistamines are the agents of choice.
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PMID:Pharmacotherapy of Parkinson's disease. 32 45

An open cross-over study of 20 patients with Parkinson's disease performed with two drugs containing L-dopa and a peripheral aromatic amino acid decarboxylase inhibitor (benserazide, carbidopa) confirmed the conclusions reached in other clinical trials that this combined treatment of Parkinson's disease is the most effective form of drug therapy available at present. With both drugs, Madopar or Sinemet, an optimum therapeutic result was obtained with relatively small doses of L-dopa (the reduction in L-dopa dosage amounting to about 80%). A loss of efficacy with both drugs, which has observed during long-term treatment of patients with Parkinson's disease, could be avoided by switching the patients from Sinemet to Madopar and vice versa. Determination of L-dopa in the plasma demonstrated that with either drug similar plasma levels of L-dopa were achieved during clinically effective treatment.
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PMID:[The combined treatment of Parkinson's disease with L-dopa plus decarboxylase inhibitors (carbidopa, benserazide) (author's transl)]. 45 2

1. Benserazide and carbidopa, decarboxylase inhibitors used in the treatment of Parkinson's disease, have been shown to inhibit the enzyme kynurenine hydrolase in rat and mouse liver. This results in reduced synthesis of nicotinamide coenzymes from tryptophan, and hence an increased reliance on dietary niacin. 2. Pellagra might be expected as a result of this inhibition of endogenous synthesis of nicotinamide nucleotides, but has not been reported in patients treated with either drug. 3. The urinary excretion of N1-methyl-nicotinamide, a product of nicotinamide nucleotide metabolism, is considerably reduced in patients treated with dopa alone or in combination with an inhibitor of peripheral dopa decarboxylase, to as low as 40% of the control value. This means that many of these patients could be classified as 'at risk' of niacin deficiency, even if not frankly deficient. 4. Patients treated with dopa plus a decarboxylase inhibitor, but not those treated with dopa alone, also show a reduced excretion of xanthurenic acid, and an increased excretion of kynurenine, as would be expected after inhibition of the kynurenine pathway, and possibly indicative of marginal vitamin B6 deficiency.
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PMID:Niacin depletion in Parkinsonian patients treated with L-dopa, benserazide and carbidopa. 47 87

Bromocriptine in high doses (up to 100 mg per day) was administered to 14 patients with advanced Parkinson's disease whose disorder was progressing despite optimum treatment with levodopa combined with a peripheral dopa decarboxylase inhibitor (carbidopa). In 10, bromocriptine (mean dose, 57 mg) induced a statistically significant (P less than 0.01) improvement in rigidity, tremor, bradykinesia, gait disturbance and total score. In seven patients levodopa with carbidopa was completely replaced by bromocriptine (mean dose, 70 mg), with improvement in four. Adverse effects were similar to those observed with levodopa and carbidopa, except that in individual patients abnormal involuntary movements and diurnal oscillations in performance (on-off effect) were decreased whereas orthostatic hypotension and mental changes were increased. Bromocriptine appears to be a major new agent in Parkinson's disease that is especially promising in patients no longer responding to levodopa.
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PMID:Treatment of parkinson's disease with bromocriptine. 98 85

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

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

We studied the histories of 173 patients with Parkinson's disease (1985-1987) chronically treated with levodopa + dopa decarboxylase inhibitor. Ninety four patients had daily motor fluctuations and 79 showed stable motor response. The most significant differences between fluctuating and stable patients were given by age at disease onset and duration of levodopa therapy. Patient with disease onset before 60 had a greater risk (p less than 0.001) of developing fluctuations. Delaying the initiation of levodopa treatment was not associated with a smaller incidence of fluctuations.
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PMID:[Motor fluctuations in Parkinson disease: risk factors]. 138 97

Marked advances in the treatment of neurological disorders which affect the elderly have been established in recent years. Cerebrovascular disorders including stroke and vascular dementia are still among the most frequent diseases in the Japanese elderly. For treatment of hypertensive patients with or without a history of stroke, slight decrease of blood pressure (BP) is recommended since recent PET studies have revealed that an excessive drop of BP markedly decreases cerebral blood flow. Furthermore, 24-hour-monitoring of BP revealed that physiological fluctuation of BP consisting of high daytime BP and low nocturnal BP disappears in hypertensive patients with vascular dementia and those with non-symptomatic vascular lesions on MRI. Recommendable BP levels for the hypertensive elderly must be established. The efficacy of both aspirin and ticlopidine for prevention of stroke has been established. Recent multi-centric trials have revealed that ticlopidine is more effective in preventing stroke but has more dangerous adverse effects than aspirin. Aspirin is reported to improve both the intellectual scale and cerebral blood flow in vascular dementia. In Parkinson's disease (PD), L-DOPA therapy, usually in combination with a dopa decarboxylase inhibitor, is common. Other dopaminergic drugs including bromocriptine, lisuride and pergolide are used clinically or are being studied. Recently selective monoamine oxidase (MAO) B inhibitors have been used in order to slow clinical progression of the disease, in addition to an attempt to increase the potential of dopamine through inhibition of MAO. Neural transplants to the striatum of PD were first applied using autografts of the adrenal medulla in 1985, but resulted in transient or only slight improvements.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Recent therapeutic advances in geriatric neurology]. 143 48


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