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)

Owing to a lack of knowledge of the pathophysiology and pathochemistry of Parkinson's disease, conservative treatment was long restricted to the treatment of symptoms. In recent decades, as the role of dopamine became better known, progressive improvements in therapy were achieved, which initially meant the administration of the precursor, L-Dopa, of the primarily non-replaceable neurotransmitter, and later augmentation of the activity of dopamine in addition. Amantadine, a highly effective drug with a wide spectrum of action and a high level of tolerability, was successfully introduced in 1969. The recently discovered NMDA antagonism, also in conjunction with a description of the mechanism of action of amantadine, which makes it possible to inhibit the effect of excitatory amino acids--in particular glutamate--in the CNS, led to the principle of neuro-protection, which is now considered the key to the treatment of Parkinson's disease.
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PMID:[Parkinson therapy yesterday, today, tomorrow. Neuroprotection gains in importance]. 147 95

The source and site of the DOPA decarboxylation to dopamine in Parkinson's disease (PD) and animal models of PD are controversial. Since most of aromatic L-amino acid decarboxylase (AADC) are lost along with the degenerating dopaminergic neurons, we addressed the possibility that other decarboxylases or a novel protein that is structurally different from AADC decarboxylate L-DOPA in the denervated striatum. Immunotitration of the extracts from the denervated striatum with AADC antibody showed that all activity can be attributed to AADC-immunoreactive protein. We then investigated if there are non-dopaminergic intrinsic striatal neurons that express AADC. No evidence of such neurons was noted by immunocytochemistry and in situ hybridization.
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PMID:Dopa-decarboxylation in the striata of rats with unilateral substantia nigra lesions. 148 Mar 24

The article summarizes historical aspects and current concepts of the treatment of Parkinson's disease. Antiparkinsonian therapy varies with the progression of the disease, age and clinical subtypes. Levodopa, anticholinergic substances, direct dopamine agonists, amantadine, L-deprenyl are used to treat motor symptoms of Parkinson's disease. Novel substances and therapeutic concepts are currently investigated. Treatment of non-motor symptoms of Parkinson's disease and supportive therapies are discussed in the article.
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PMID:Modern therapy of Parkinson's disease. 149 Dec 45

Advance in understanding of the anatomy, physiology and pharmacology of basal ganglia organisation over the past decade revealed a functional relation between excitatory glutamatergic and the degenerated dopaminergic nigrostriatal transmitter systems which could serve as targets for pharmacological interventions in Parkinson's disease. The selective AMPA-antagonist NBQX is not effective in animal models of Parkinson's disease when given alone but ameliorates parkinsonian symptomatology and enhances the locomotor response of a threshold dose of L-DOPA. These synergistic effects are seen in the MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmoset and the rat with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra. Here we report that, in the latter model, such synergism of NBQX is also seen with the direct dopamine agonists lisuride and apomorphine, indicating the potential usefulness of AMPA antagonists for the symptomatic treatment of Parkinson's disease.
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PMID:Synergism of NBQX with dopamine agonists in the 6-OHDA rat model of Parkinson's disease. 149 Dec 48

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to dogs produces clinical, pathological and neurological features in dog resembling human Parkinson's disease. Using this animal model, we studied the changes in diurnal rhythms of urine volume, creatinine in urine, and vasopressin, aldosterone and renin activity in plasma. Before MPTP treatment, urine volume showed a peak between 17.00 and 1.00 and plasma vasopressin concentration also showed a clear circadian rhythm with a peak at 13.00 and a minimum level at 5.00. Two weeks after MPTP treatment (2.5 mg/kg i.v.), the rhythm of urine volume disappeared and that of vasopressin became less clear. Plasma renin activity increased 2 and 4 weeks after MPTP treatment. The increase was, however, not enough to change the concentration of plasma aldosterone. We examined the effect of L-3,4-dihydroxyphenylalanine (levodopa), on the circadian pattern of urine volume and vasopressin attenuated by MPTP. Levodopa (4 mg/kg/day) was administered orally every day from the first week after MPTP treatment. The circadian rhythms of urine volume and vasopressin reappeared within one week after the start of levodopa administration.
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PMID:Disappearance of circadian rhythms in Parkinson's disease model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in dogs. 150 21

Tolerability is one of the main problems of the long-term use of antiparkinsonian drugs, especially in the advanced stages of Parkinson's disease. Since 1988, we have performed a prospective study to assess the clinical and therapeutic factors which may influence the tolerability of a new antiparkinsonian drug, selegiline. 168 patients, with a mean age of 68, were treated with selegiline in combination with L-Dopa or with L-Dopa and a dopamine agonist (bromocriptine, lisuride or piribedil). After an average of 19 months, 23 adverse effects (13.7%) were noted during the first three months of treatment with selegiline. Discontinuation was required in only 10 cases (5.9%) with 9 out of 10 for a psychotic episode. Neither age, nor the stage of the disease, nor the dose of levodopa in combination with selegiline or the presence of mental disturbances seemed to be predicting factors for appearance of a psychic episode. If selegiline with levodopa or with bromocriptine and levodopa appeared to be safe antiparkinsonian combinations, significant psychic side effects occurred with piribedil in combinations with selegiline and levodopa. A possible explanation was that selegiline potentiates piribedil side-effects.
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PMID:[Long-term selegiline tolerance in the treatment of Parkinson's disease]. 152 99

Parkinson's disease, or paralysis agitans, is a central nervous system disease. Concentrations of dopamine and acetylcholine, neurotransmitters in the substantia nigra of the basal ganglia, become imbalanced. Bradykinesia, rigidity, rhythmic head nodding, and pill-rolling motion of the thumb and forefinger are characteristic. Difficulty verbalizing, dementia, and depression are also common. Levodopa, the medication of choice, restores dopamine to brain cells, reducing parkinsonian symptoms. Awareness by the PACU nurse of the potential for systemic effects of dopamine is one important element of postanesthesia care for the patient with Parkinson's disease. In addition, recognition of the unique physical limitations and medication combinations for each patient promotes optimal postanesthesia nursing assessment and intervention.
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PMID:The postanesthesia patient with Parkinson's disease. 153 Dec 38

L-DOPA is frequently used to relieve symptoms of Parkinson's disease (PD), but its use in patients with more advanced PD is complicated by on-off phenomena. We used simultaneous microdialysis of striatum and ipsilateral substantia nigra to characterize changes in extracellular fluid (ecf) levels of dopamine (DA) following systemic treatment with L-DOPA (25 mg/kg as methylester) in awake, normal rats and those with partial (less than 99%) or complete (greater than 99%) DA depleting unilateral lesions of the nigrostriatal pathway (nsp). In normal rats, nigral ecf DA rose 17-fold above baseline after L-DOPA, compared to a 2.6-fold increase in normal striata. Striatal ecf DA rose equally after L-DOPA in all three groups, whereas peak nigral ecf DA in completely lesioned rats was three times that in normal or partially lesioned animals. Peak nigral ecf DA in completely lesioned rats exceeded striatal ecf DA in all groups by almost 2-fold. Activity after L-DOPA was biphasic ("hyperkinetic/bradykinetic") in completely lesioned but not in normal or partially lesioned animals, and the reduced activity occurred 2.5-4 h after L-DOPA at a time when both nigral and striatal ecf DA levels were still elevated. L-DOPA-induced increases in activity were predictable by greater elevations in nigral compared to striatal ecf DA in animals with complete lesions of the nigrostriatal pathway. Post-DOPA reduced activity might result from desensitization of synaptic events mediated by DA receptors; this may underlie DOPA-related on-off phenomena in patients with advanced PD.
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PMID:Simultaneous microdialysis in striatum and substantia nigra suggests that the nigra is a major site of action of L-dihydroxyphenylalanine in the "hemiparkinsonian" rat. 153 96

Levodopa is effective in relieving symptoms of Parkinson's disease. However, long-term complications make sustained control problematic. Most management problems are related to the pharmacokinetic and pharmacodynamic properties of levodopa. Careful titration based on pharmacologic principles may achieve optimal therapeutic effects.
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PMID:Pharmacokinetics and pharmacodynamics of levodopa. 154 97

Clinical evidence suggests that deprenyl may slow progression of Parkinson's disease, although mechanisms underlying this putative neuroprotective action remain poorly understood. To address this issue, we studied deprenyl in 12 parkinsonian patients using a single-blind, placebo-controlled, crossover design. After 1 month, deprenyl (10 mg/d) decreased the optimal levodopa requirement by 24% (oral) and 16% (intravenous). Levodopa-induced dyskinesias were prolonged by 430%, and antiparkinsonian action by 44%. Mood improved by 47%. One month after withdrawing deprenyl, effects on dyskinesias and mood had yet to return to baseline. There was no change in activities of circulating glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, and catalase, nor in levels of lipid peroxide and vitamin E. Deprenyl also failed to modify CSF levels of total glutathione and activities of glutathione peroxidase or superoxide dismutase. These effects on levodopa pharmacodynamics and mood complicate the interpretation of available investigations of deprenyl's neuroprotective action and increase the risk of adverse effects of levodopa.
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PMID:Deprenyl effects on levodopa pharmacodynamics, mood, and free radical scavenging. 154 14


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