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)

Amantadine has been used since 1969 in the treatment of Parkinson's disease. In 1970, were described the special symptoms noted in the lower limbs due to this drug. The authors, after a review of the various disturbances, have studied 10 cases by Capillaroscopy. They emphasize the interest of the study of this abnormality of the micro-circulation, producing vaso-constriction of the arterioles and venules.
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PMID:[Circulatory disorders induced by amantidine]. 18 58

Amantadine is a putative dopaminergic compound known to be therapeutically effective in idiopathic and postencephalitic Parkinson's disease. In a double-blind placebo-controlled crossover study of 39 psychiatric inpatients, amantadine and trihexyphenidyl were equally effective in treating drug-induced parkinsonism, and amantadine produced fewer and less severe side effects. The authors suggest that amantadine is an effective alternative to atropine-like agents, with fewer implications for long-term risk of tardive dyskinesia.
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PMID:Amantadine versus trihexyphenidyl in the treatment of neuroleptic-induced parkinsonism. 78 62

A double-blind, placebo-controlled, crossover study with long-term follow-up of amantadien i- Parkinson's disease was performed on 26 patients. Other antiparkinsonian medications were discontinued in all but three patients. Amantadine resulted in a statistically significant 12 percent overall improvement over placebo. Twenty of 26 patients, without breaking the code, selected amantadine for long-term usage. Ten patients continued treatment for 10 to 12 months, and an overall statistically significant improvement was noted at 2 weeks and at 1, 2, 3, and 10 to 12 months. Improvements in tremor and rigidity remained relatively constant, while there was some apparent loss of efficacy in timed tests and quality of timed tests. Amantadine appears effective in the long-term treatment of some patients with Parkinson's disease.
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PMID:Amantadine in Parkinson's disease. A double-blind, placebo-controlled, crossover study with long-term follow-up. 80 67

Twenty-three patients with Parkinson's disease participated in long-term, double-blind evaluations of the effectiveness and side effects of amantadine in combination with levodopa therapy. Sixteen patients completed the year-long study, which consisted of randomized crossover of amantadine and placebo before levodopa was begun and again after 5 and 11 months of continuous levodopa therapy. Initially, 16 of 23 patients (70 percent) had a favorable response to amantadine during the first crossover period. After 1 year of levodopa, at least eight of 16 patients (50 percent) responded favorably to amantadine compared with placebo. Some of the amantadine responders previously had been nonresponders, and vice versa. The response to amantadine was quantitatively similar in the responders even after the patients had been receiving levodopa therapy. Amantadine should be tried as a therapeutic agent in addition to levodopa for parkinsonism if more beneficial effect is desired, even if amantadine was previously ineffective in the same patient.
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PMID:Long-term evaluation of amantadine and levodopa combination in parkinsonism by double-blind corssover analyses. 80 69

The N-methyl-D-aspartic acid (NMDA) receptor is an intriguing target for the development of drugs with anti-Parkinsonian activity as well as with protective actions against degenerative processes induced by brain ischemia. Amantadine is used in the treatment of Parkinson's disease without a well established mechanism of action. We show here that amantadine inhibits, in a non-competitive way, the NMDA receptor-mediated stimulation of acetylcholine release from rat neostriatum in vitro in "therapeutic" (i.e., low micromolar) concentrations. This indicates that amantadine might exert its anti-Parkinsonian effect via blockade of NMDA receptors. Sustained stimulation of NMDA receptors induces so-called excitotoxicity. Recently, it was demonstrated that amantadine is able to inhibit NMDA induced cell death in a neuronal culture. On the basis of these findings it seems worth investigating if amantadine is also able to protect against neurodegenerative processes caused by brain ischemia in vivo.
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PMID:Amantadine as N-methyl-D-aspartic acid receptor antagonist: new possibilities for therapeutic applications? 132 May 14

The triad of rigidity, fever, and elevation of serum creatine phosphokinase (CPK) levels, labeled 'neuroleptic malignant syndrome' (NMS), is a dangerous complication of neuroleptic drug treatment. Amantadine was introduced for the pharmacological management of NMS because of its beneficial effects in Parkinson's disease which were attributed to direct or indirect dopaminomimetic properties of amantadine. While the dopaminomimetic effects of amantadine are weak under experimental conditions, recent studies have confirmed that amantadine is an antagonist at the N-methyl-D-aspartate (NMDA) type of glutamate receptor. Two lines of evidence suggest that amantadine or other NMDA receptor antagonists could be effective drugs for the reversal of NMS symptoms. First, glutamate antagonists restore the balance between glutamatergic and dopaminergic systems when dopaminergic transmission has been antagonized by neuroleptic drugs. Second, by virtue of their effects against rigor and spasticity, NMDA antagonists may reduce increased muscle tone and prevent rhabdomyolysis. In conclusion, NMS may be considered an iatrogenic excitatory aminoacid syndrome which is amenable to NMDA receptor antagonist therapy.
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PMID:A rationale for NMDA receptor antagonist therapy of the neuroleptic malignant syndrome. 133 36

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

Amantadine is generally used in the prophylaxis of infection with influenza A, in the treatment of Parkinson's disease and in the treatment of neuroleptic side effects. In this study acute effects of amantadine infusions on event-related potentials (ERP) were studied in 20 mildly demented patients diagnosed according to DSM-III-R criteria. Each patient was treated, in randomized order, with 0.2 g amantadine-sulfate in 500 ml NaCl and 500 ml NaCl placebo, i.v. over one hour with an interval of two weeks in-between. ERPs were investigated in an auditory odd-ball paradigm before as well as 5 hours after the infusion. In addition to 17 EEG records, vertical and horizontal EOGs were recorded. After EOG-minimization and visual artifact rejection the peak latencies of the spatial average were determined by an automatic procedure. There was no effect of amantadine on ERP latencies. N1 of the non-target showed a trend towards amplitude augmentation, P2 amplitude was reduced. As compared to placebo, P300 amplitude of targets was significantly augmented by 3.1 microV (30% of pre-treatment value), confirming the hypothesis that amantadine may influence the P 300 amplitude in the sense of an improved availability of cognitive processing resources.
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PMID:Topographic mapping of long latency "cognitive" event-related potentials (P 300): a double-blind, placebo-controlled study with amantadine in mild dementia. 138 2

N-Methyl-D-aspartate (NMDA) receptor activation has been implicated in the pathogenesis and clinical expression of Parkinson's disease. Because some antiparkinsonian drugs have NMDA antagonist properties, we examined their effects on NMDA toxicity, measured by lactate dehydrogenase (LDH) release, in neuron-enriched cerebrocortical cultures. Amantadine reduced NMDA toxicity with half-maximal reduction at approximately 30 microM, while trihexphenidyl, L-3,4-dihydroxyphenylalanine (L-DOPA), bromocriptine and selegiline were ineffective, and benztropine was itself toxic. Amantadine and related drugs could not only reduce parkinsonian symptoms, but also modify underlying neurodegenerative processes.
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PMID:Antiparkinsonian drugs and in vitro excitotoxicity. 147 27

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


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