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)

Degeneration of dopaminergic nigrostriatal neurons in primate models of Parkinson's disease (PD) leads to an overactivity of excitatory glutamatergic projections from the subthalamic nucleus (STN) to the output nuclei of the basal ganglia resulting in rigidity and akinesia. The selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonist 6-nitro-sulfamoyl-benzo-quinoxaline-dione (NBQX) and the competitive N-methyl-D-aspartate (NMDA) antagonist 3-carboxy-piperazin-propyl phosphonic acid (CPP) ameliorate parkinsonian symptomatology when co-administered with threshold doses of L-DOPA in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets and induce rotations in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra (SN). Here we report that in the 6-OHDA-lesioned rat NBQX and CPP induce contralateral rotations when combined with threshold doses of the direct dopamine agonists lisuride or apomorphine. AMPA antagonists and competitive NMDA antagonists may therefore be suitable as adjuvants for the treatment of PD.
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PMID:NBQX (6-nitro-sulfamoyl-benzo-quinoxaline-dione) and CPP (3-carboxy-piperazin-propyl phosphonic acid) potentiate dopamine agonist induced rotations in substantia nigra lesioned rats. 128 Jul 93

Pulmonary function tests were performed before and at different times after 250 mg L-Dopa in 12 patients with Parkinson's disease (PD). Six were de-novo patients, the other six patients had been taking L-Dopa over different periods. All patients had an abnormal basal flow-volume loop, which significantly improved only in de-novo patients. This improvement occurred early and was independent on improvement of neurological symptoms. The effect of L-Dopa on pulmonary function could be a useful test in differentiating PD from related extrapyramidal syndromes.
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PMID:Upper airway muscles dysfunction and levodopa responsiveness in Parkinson's disease. 129 93

Superoxide dismutase (SOD) activities in Parkinson's disease (PD) were significantly lower than those in controls, especially in a treated PD group. However, SOD activities in an untreated PD group did not decrease. There was a significant correlation between SOD activities and the duration of illness in the treated PD group (p < 0.05). There was a significant correlation between SOD activities and the present doses of L-DOPA/carbidopa in the treated PD group.
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PMID:Decreased superoxide dismutase activity in erythrocyte in Parkinson's disease. 130 19

Levodopa-induced dyskinesias are a common complication of chronic dopaminergic therapy in patients with Parkinson's disease (PD). The overall prevalence of levodopa-induced dyskinesias ranges from 40%-90% and is related to the underlying disease process, pharmacologic factors, and to the duration of high dose levodopa therapy. The mechanisms underlying the emergence of levodopa-induced dyskinesias are unknown, although most investigators favor the theory that striatal dopamine receptor supersensitivity is directly responsible for the development of these abnormal movements. In laboratory animals, the pineal hormone melatonin has been shown to regulate striatal dopaminergic activity and block levodopa-induced dyskinesias (Cotzias et al., 1971). Since the pineal gland is known to be a magnetosensitive organ and as application of external magnetic fields has been shown to alter melatonin secretion, we studied the effects of application of external artificial weak magnetic fields in a Parkinsonian patient with severe levodopa-induced dyskinesias ("on-off"). Application of weak magnetic fields with a frequency of 2 Hz and intensity of 7.5 picotesla (pT) for a 6 minute period resulted in a rapid and dramatic attenuation of Parkinsonian disability and an almost complete resolution of the dyskinesias. This effect persisted for about 72 hours after which the patient regressed to his pretreatment state. To ascertain if the responses elicited in the laboratory were reproducible, the patient was instructed to apply magnetic fields of the same characteristics daily at home. These subsequent treatments paralleled the initial response with a sustained improvement being maintained during an observation period lasting at least one month. This case demonstrates the efficacy of weak magnetic fields in the treatment of Parkinsonism and motor complications of chronic levodopa therapy.
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PMID:Magnetic fields in the treatment of Parkinson's disease. 134 26

Continuous dopaminergic stimulation has been shown to stabilize motor fluctuations in patients with advanced Parkinson's disease (PD) who do not respond to more conventional forms of therapy. Levodopa infusions confer immediate benefit as a direct result of maintaining steady plasma levodopa concentrations. Fluctuations of synaptic dopamine inherent in the usual oral treatment of PD might result in deleterious postsynaptic changes. Some of these presumed receptor alterations might revert as a consequence of continuous levodopa infusion.
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PMID:The rationale for continuous dopaminergic stimulation in patients with Parkinson's disease. 134 8

Treatment of Parkinson's disease (PD) can be divided into two categories: symptomatic therapy (restoring dopamine levels toward normal and reversing functional disability) and preventive therapy (interfering with the pathophysiologic mechanism of PD to prevent or decrease the rate of progression of the disease). Regarding symptomatic treatment, although anticholinergic preparations generally are considered effective for the symptoms of tremor and rigidity without altering bradykinesia, their effectiveness is limited and adverse reactions are common; their role should be restricted to use as adjuvants to levodopa therapy. Amantadine has been shown to be as effective as anticholinergics, but it lacks long-term efficacy. Dopamine agonists--bromocriptine, pergolide mesylate and lisuride in Europe--are not as effective as levodopa and therefore rarely are used as initial therapy; their proposed role, too, is as adjuvants to levodopa therapy. Levodopa is the most effective drug presently available for the treatment of PD; its introduction is accompanied by rapid and dramatic reduction of symptoms and signs. Initial adverse reactions are not usually a major problem; and although there is speculation that initiation of therapy should be delayed because of possible long-term complications, clinically distinguishing these from problems related to disease progression itself is difficult. The possibility that nigral cell death is mediated by oxidative mechanisms provides the basis for considering antioxidant therapy as protective treatment; selegiline, an antioxidant, has been found to delay the need for symptomatic therapy. It is suggested that initial treatment of Parkinson's disease begin with both preventive therapy with selegiline and symptomatic treatment with the sustained-release preparation of levodopa, which may be associated with fewer long-term complications.
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PMID:Initiating treatment of Parkinson's disease. 134 9

Levodopa is the most potent symptomatic treatment for Parkinson's disease but adverse reactions are common and the initial response is not maintained. Further there is recent evidence that suggests that free radicals generated from the oxidative metabolism of dopamine may contribute to the pathogenesis of Parkinson's disease. This raises the possibility that levodopa therapy by way of its conversion to dopamine may promote free radical formation and accelerate the rate of neuronal damage. Levodopa sparing strategies designed to minimize the cumulative levodopa dosage employed over the course of the disease seem a rational way to treat Parkinson patients in face of current information. Such a strategy would include the use of dopamine agonists as primary symptomatic therapy, the introduction of levodopa as an adjunct when dopamine agonists can no longer sufficiently provide satisfactory clinical control and the use of the lowest dose of levodopa that will provide satisfactory clinical control. In this way symptomatic control is not compromised on theoretical grounds, but the cumulative levodopa dose is minimized in an effort to reduce the likelihood of free radical formation with their potential adverse consequences on disease progression.
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PMID:A rationale for dopamine agonists as primary therapy for Parkinson's disease. 134 62

The addition of a D2 agonist such as bromocriptine to L-Dopa therapy can often improve the response of patients with Parkinson's disease dramatically. Simultaneous activation of D1 and D2 dopamine receptors can produce a synergistic effect on locomotion in rats and primates. However, despite the importance of this addition of a D2 agonist to the D1/D2 agonist L-Dopa, little is known of the sites of action of these agents. Recent work suggests that, in addition to D1 and D2 dopamine receptor sites in the striatum (caudate-putamen), L-Dopa and D1 agonists have important effects at D1 dopamine receptors in the substantia nigra. Animal experiments suggest that D1 and D2 dopamine receptor agonists probably also affect different outflow pathways from the striatum. An understanding of these pathways and how dopamine agonists affect them gives insight into some of the clinical problems experienced in treating Parkinson's disease (the "on-off" phenomenon, for example). D1/D2 dopamine receptors also differentially affect gene expression and regulation in the striatum. An understanding of the anatomical and biochemical location of the actions of dopamine receptor agonists will be important in maximizing the beneficial effects and minimizing the side-effects of both presently-used drugs and new treatments.
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PMID:Synergistic interactions of D1- and D2-selective dopamine agonists in animal models for Parkinson's disease: sites of action and implications for the pathogenesis of dyskinesias. 134 63

The use of the dopamine receptor agonists in Parkinson's disease has a compelling logic. These agents are supposed to act independently of the dying cells of the substantia nigra directly on the cells of the striatum. Early clinical trials in advanced disease were only mildly impressive. Later they were found to be beneficial in early disease but their effectiveness waned. Their ultimate failure may reflect the fact that the majority of current agents do not stimulate D1 and D2 receptors in a physiologic ratio. The drugs may act presynaptically and with the eventual loss of the anatomic relationships between nigra and striatum the drugs fail. There is, however, a rationale to their current use. When used along with L-Dopa in early disease the development of late-stage fluctuations are reduced with the same anti-parkinsonian benefits. Merging this concept with the demonstrated effect of selegiline in slowing the course of the disease, the current practice of triple therapy with selegiline, L-Dopa and a dopamine receptor agonist emerges.
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PMID:The place of the dopaminergic agonists in the treatment of Parkinson's disease: the view from the trenches. 134 64

Levodopa-induced dyskinesias (LID) in Parkinson's disease (PD) may be classified into three main categories: "On" dyskinesias, diphasic dyskinesias (DD), and "off" periods. The study of 168 parkinsonian patients showed that about half (n = 84) showed one pattern of LID only. A combination of two was present in 68, and 16 had the three presentation patterns. A fairly good correlation between type of dyskinesia and presentation pattern was established. Chorea, myoclonus, and dystonic movements occurred during the "on" period. Dystonic postures, particularly affecting the feet, were mainly present in the "off" period, but a few patients had a diphasic presentation. Repetitive stereotyped movements of the lower limbs always corresponded to DD. Acute pharmacological tests using dopamine agonists (subcutaneous apomorphine 3-8 mg; intravenous lisuride 0.1-0.15 mg) and dopamine antagonists (intravenous sulpiride 200-400 mg and intravenous chlorpromazine 25 mg) were performed in 40 patients. Dopamine agonists enhanced "on" dyskinesias and markedly reduced or abolished "off" period dystonia and DD. Dopamine antagonists reduced all types of LID but usually aggravated parkinsonism. These clinical and pharmacological results indicate that LID in PD are a heterogeneous phenomenon difficult to explain on the basis of a single pathophysiological mechanism.
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PMID:Levodopa-induced dyskinesias in Parkinson's disease: clinical and pharmacological classification. 135 58


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