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)

(-)Deprenyl (Selegiline, Jumex, Eldepryl, Movergan), a close structural relative to phenylethylamine (PEA), is a drug of a unique pharmacological spectrum. (a) It is highly potent and selective irreversible inhibitor of B-type monoamine oxidase (MAO), a predominantly glial enzyme in the brain, the activity of which significantly increases with age. (-)Deprenyl was the first selective inhibitor of MAO-B described in literature, became the worldwide research tool used for blocking selectively B-type MAO, and is still the only MAO-B inhibitor in clinical use. (b) (-)Deprenyl interferes with the uptake of catecholamines and indirectly acting sympathomimetics because it is handled by the catecholaminergic neuron similarly to the physiological substances transported through the axonal end-organ and vesicular membrane. The unique behavior of (-)deprenyl is that, in striking contrast to PEA and its relatives, it does not push the transmitter from the storage places, i.e., it is not a releaser. The net result is that (-)deprenyl inhibits the releasing effect of tyramine and is presently the only safe MAO inhibitor which can be administered without dietary restrictions. (c) Maintenance on (-)deprenyl enhances selectively superoxide dismutase (SOD) and catalase activity in the striatum. This effect is unrelated to the MAO and uptake inhibitory effects of the drug. (d) Maintenance on (-)deprenyl facilitates the activity of the nigrostriatal dopaminergic neurons with remarkable selectivity. This effect is also unrelated to either the MAO or the uptake inhibitory effects of the drug. All in all, (-)deprenyl maintains the activity of the nigrostriatal dopaminergic machinery on a higher activity level and slows down its age-related decline. Male rats maintained on (-)deprenyl lost their capacity to ejaculate later, retained their learning ability longer, and lived longer than their saline-treated peers. Parkinsonians on levodopa plus (-)deprenyl (10 mg daily) lived significantly longer than those on levodopa alone. (-)Deprenyl is the first drug which retards the progress of Parkinson's disease. Freshly diagnosed parkinsonians maintained on (-)deprenyl did not require levodopa until significantly later than their placebo-treated peers. Maintenance on (-)deprenyl significantly improved the performance of patients with Alzheimer's disease. It is concluded that in Parkinson's disease and Alzheimer's disease patients need to be treated daily with 10 mg (-)deprenyl from diagnosis until death, irrespective of other medication.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacological basis of the therapeutic effect of (-)deprenyl in age-related neurological diseases. 151 86

Selegiline (Eldepryl), recently approved as an adjunct to levodopa-carbidopa (Sinemet), was administered to eight patients with Parkinson's disease in an open-label study. Many side effects were seen pertinent in particular to the elderly patient. Urinary retention was precipitated in two gentlemen. We advise that this medication be used with caution in the parkinsonian patient.
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PMID:Side effects of selegiline (Eldepryl). 157 Oct 71

(-)Deprenyl (Selegiline, Jumex, Eldepryl, Movergan), a close structural relative to phenylethylamine (PEA), is a drug with a unique pharmacological spectrum. (1) It is a highly potent and selective, irreversible inhibitor of B-type monoamine oxidase (MAO), a predominantly glial enzyme in the brain. The activity of this enzyme significantly increases with age. (-)Deprenyl, the first selective inhibitor of MAO-B described in literature, has become the universally used research tool for selectively blocking B-type MAO. It is the only MAO-B inhibitor in clinical use. (2) (-)Deprenyl interferes with the uptake of catecholamines and indirectly acting sympathomimetics because it is handled by the catecholaminergic neuron in a way similar to the physiological substances transported through the axonal end organ and vesicular membrane. The unique behavior of (-)deprenyl is that, in striking contrast to PEA and its relatives, it does not displace the transmitter from storage, ie, it is not a releaser. The net result is that (-)deprenyl inhibits the releasing effect of tyramine, and, at present, is the only safe MAO inhibitor that can be administered without dietary precautions. (3) Maintenance on (-)deprenyl selectively enhances superoxide dismutase (SOD) and catalase activity in the striatum. This effect is unrelated to its effect on MAO-B and the inhibitory effects of the drug on neurotransmitter uptake. (4) Maintenance on (-)deprenyl facilitates the activity of the nigrostriatal dopaminergic neurons with remarkable selectivity, and this effect, too, is unrelated to either its effects on MAO or on neurotransmitter uptake. (5) Maintenance on (-)deprenyl prevents the characteristic age-related morphological changes in the neuromelanin granules of the neurocytes in the substantia nigra. All in all, (-)deprenyl increases the activity of the nigrostriatal dopaminergic system and slows its age-related decline. Maintenance of male rats on (-)deprenyl delays the loss of the capacity to ejaculate, slows the decline of learning and memory, and significantly lengthens the life-span as compared with saline-treated rats. Parkinson's disease patients on levodopa plus (-)deprenyl (10 mg daily) live significantly longer than those on levodopa alone. (-)Deprenyl is the first drug that retards the progress of Parkinson's disease. Newly diagnosed Parkinson's disease patients maintained on (-)deprenyl need levodopa significantly later than their placebo-treated peers. Maintenance on (-)deprenyl improves significantly the performance of patients with Alzheimer's disease. It is concluded that Parkinson's disease and Alzheimer's disease patients need to be treated daily with 10 mg (-)deprenyl from diagnosis until death, irrespective of other medication.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:(-)Deprenyl-medication: a strategy to modulate the age-related decline of the striatal dopaminergic system. 163 30

We compared the results of treatment with selegiline (deprenyl, Eldepryl) in 17 patients with advanced Stage 4 Parkinson Disease (PD) who were on levodopa (as Sinemet) with 65 Stage 2 or 3 patients with early PD who were also on levodopa. The first group consisted of 17 patients with advanced Stage 4 PD without response fluctuations ("wearing off" or "on off" phenomena). Their mean age was 72.1 +/- 7.5 years, their mean duration of PD was 7.4 +/- 3.2 years. The second group consisted of 65 patients with Stage 2 or 3 PD who had recently been started on levodopa. Their mean age was 63 +/- 12.1 years, their mean duration of PD was 7.4 +/- 3.2 years. The mean dose of selegiline was 10.0 +/- 1.8 mg per day (range 5-20 mg). The mean duration of treatment was 1.5 +/- 0.8 years. During the four years of observation 55.3 +/- 8.0% of the Stage 2 or 3 patients improved while only 14.3 +/- 13.5% of the Stage 4 patients improved. This difference was significant (p less than 0.05). During this time 22.0 +/- 6.7% of the Stage 2 or 3 patients worsened and 60.7 +/- of the Stage 4 patients worsened. This degree of worsening was significant (p less than 0.05). Adverse effects were minor and reversible. Our observations suggest that selegiline is more effective (higher percent of patients improving, lower percent of patients worsening) when it is added earlier with patients on levodopa than when it is added later.
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PMID:Experience with selegiline and levodopa in advanced Parkinson's disease. 180 39

Parkinson's disease affects thousands of Americans, men and women equally and apparently with little regard to race. Its diagnosis depends largely on repeated clinical observations of representative signs, such as resting tremor, rigidity, bradykinesia, and gait disturbances. Patients progress through stages: Early disease involves only one limb or side and confers minimal disability, but advanced disease restricts patients to full care. Treatment is chosen on the basis of disease stage and patient response. Combination carbidopa-levodopa (Sinemet) is appropriate for any significant degree of disability, and other antiparkinsonian drugs and anticholinergic agents may be used as adjuncts. Electroconvulsive therapy, use of selegiline hydrochloride (Eldepryl), and surgery are still undergoing investigation but may hold promise.
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PMID:Treating the progressive stages of Parkinson's disease. 190 7

L-deprenyl (Eldepryl) added to Sinemet CR in the treatment regimens of seven patients with Parkinson's disease (PD) and therapeutic response fluctuations (RF) allowed a statistically significant reduction in total daily levodopa intake and an increase in the mean interdose interval. Trends were noted towards a reduction in the number of daily "off" periods and an increase in the portion of the waking day spent "on." Three patients suffered an increase in the intensity of their dyskinesias, and discontinued taking deprenyl. Four patients, all of whom reported improved functioning during "off" periods, have continued taking the combination. Sinemet CR and deprenyl can safely be used together in patients with advanced PD, and the combination may result in improved control of motor fluctuations in selected patients.
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PMID:L-deprenyl (selegiline) added to Sinemet CR in the management of Parkinson's disease patients with motor response fluctuations. 190 74

Six patients with Parkinson's disease (PD) and therapeutic response fluctuations (RF) on levodopa treatment participated in an open-label trial of L-deprenyl (Eldepryl) in conjunction with Sinemet. Deprenyl (10 mg/day) allowed a slight but not statistically significant 22% reduction of total daily levodopa intake after 4 weeks of treatment, with a significant but unsustained reduction in the number of daily "off" periods and an increase in the portion of waking day spent "on." Pharmacokinetic studies revealed no effect of deprenyl on the plasma levodopa concentration vs. time curve, or the coefficient of variation (C.V.) of plasma levodopa levels measured over an 8-h period. Plasma DOPAC levels were unaffected, suggesting that the majority of peripheral DOPAC is generated by action of MAO-A. For most patients, benefit was not maintained. Two patients have continued taking the drug, and both have enjoyed significant reductions in total levodopa dose. Both have mild end-of-dose failure and little dyskinesia. Since no changes in peripheral pharmacokinetics of levodopa could be demonstrated, any therapeutic action of deprenyl in PD would appear to be due to prolongation of dopaminergic activity within the CNS.
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PMID:L-deprenyl, levodopa pharmacokinetics, and response fluctuations in Parkinson's disease. 210 91

(-)Deprenyl (Selegilinum hydrochloricum, Jumex, Eldepryl) developed in the early sixties as a new spectrum, potent, irreversible MAO blocker (Knoll et al., 1965) was introduced as the first selective inhibitor of B-type MAO (Knoll and Magyar, 1972). In striking contrast to MAO inhibitors which strongly potentiate the pressor effect of tyramine, (-)deprenyl was described to inhibit the tyramine-induced release of noradrenaline in vascular smooth muscle (Knoll et al., 1968). The peculiar pharmacological spectrum of (-)deprenyl allowed its use as an adjuvant to the levodopa therapy of Parkinson's disease (for review see Birkmayer and Riederer, 1985). Levodopa therapy revolutionized the medication of Parkinson's disease, but severe side-effects forced the search for adjuvants with a levodopa-sparing effect. Peripheral decarboxylase inhibitors are now efficiently used for this purpose. It was reasonable to expect further potentiation and prolongation of the effect of levodopa in parkinsonians with concurrent administration of MAO inhibitors. A number of irreversible inhibitors of this type were tested in combination with levodopa, and potentiation of the antiakinetic effect of the latter was demonstrated; however, the supervention of distressing side-effect (greatly increased involuntary movements, hypertensive reactions, toxic delirium) terminated any further work along this line. There was a concensus that to give MAO inhibitors concurrently with levodopa was contra-indicated. This conclusion was called in question, however, by the development of deprenyl. (-)Deprenyl is a safe MAO inhibitor which can be given concurrently with levodopa and a peripheral decarboxylase inhibitor for the long run without the supervention of any distressing side-effects. For details regarding the pharmacology of (-)deprenyl we refer a number of reviews (Knoll 1976, 1978, 1980, 1982, 1983, 1986). The aim of this paper is to give a brief survey of the most important experimental data which demonstrate that (-)deprenyl facilitates dopaminergic tone in the brain in a peculiar manner and gives a satisfactory explanation for the observation that long-term (-)deprenyl treatment prolongs the life span of parkinsonian patients significantly (Birkmayer et al., 1985).
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PMID:The pharmacology of (-)deprenyl. 309 62

The selective monoamine oxidase (MAO) B inhibitor L-deprenyl (Eldepryl, Jumex, Movergan, Selegiline) has gained acceptance as a useful form of adjunctive therapy in the treatment of Parkinson's disease. It has recently been suggested that deprenyl might be effective in altering the course of Parkinson's disease by actually slowing its progression. The rationale for this "new therapeutic strategy" rests on several lines of evidence which can be categorized as theoretical, experimental and empirical. We present details of an "in progress" double-blind, placebo-controlled, prospective clinical drug trial using deprenyl in patients with early, untreated Parkinson's disease. This study is designed to directly test the hypothesis that deprenyl may be effective in favorably altering its natural history. Rigorously testing this new hypothesis could have a major impact on current concepts regarding the treatment and management of Parkinson's disease.
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PMID:R-(-)-deprenyl as a possible protective agent in Parkinson's disease. 312 6

In the aging brain there is a loss of neurons compensated for by a proliferation of glial cells. Because of the increased B-type monoamine oxidase (MAO) activity present in the glia, dopaminergic and 'trace aminergic' modulation in the brain declines in senescence. The significant increase of the incidence of depression in the elderly, the age-dependent decline in male sexual vigor and the frequent appearance of parkinsonian symptoms in the latter decades of life might be attributed to a decrease of dopamine and 'trace amines' in the brain. The outlines of a drug strategy to counteract these biochemical lesions of aging by chronic administration of (-)deprenyl (Jumex, Eldepryl), a selective inhibitor of B-type MAO, which facilitates dopaminergic and 'trace-aminergic' activity in the brain, are forwarded. The restitution and long-term maintenance of full scale sexual activity in aged male rats continuously treated with (-)deprenyl and the clinical observation that this drug prolongs in a statistically significant manner, the duration of the Parkinson's disease support the view that (-)deprenyl may improve deteriorating functions due to dopamine deficiency in the aging brain.
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PMID:The facilitation of dopaminergic activity in the aged brain by (-)deprenyl. A proposal for a strategy to improve the quality of life in senescence. 392 74


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