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)

We evaluated the effects of amantadine on levodopa-induced dyskinesia (LID) in eighteen consecutive Parkinson's disease (PD) patients in a randomized, double-blind, placebo-controlled study. The primary outcomes were the Clinical Dyskinesia Rating Scale (CDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) part IVa score changes. The secondary outcomes were the UPDRS II and III score changes. Amantadine did not change the CDRS score for hyperkinesia or dystonia, but decreased the duration of LID and its influence on daily activities (p=0.04) and the UPDRS II score (p=0.01) more than placebo. These findings show that amantadine reduces the duration of LID and improves motor disability in PD.
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PMID:Amantadine reduces the duration of levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study. 1615 88

Parkinson's disease (PD) is primarily a disease of elderly patients. This article reviews current knowledge and recent developments relating to drugs that can be used as alternatives to levodopa as initial treatment of PD. Synthetic orally acting dopamine agonists have found increasing favour as an option for early PD in relatively young patients. This strategy is based on evidence that this approach may delay the onset of motor fluctuations, at least during the first 5 years of treatment. Subcutaneous apomorphine infusions may attenuate motor fluctuations in late-stage disease, and transdermal rotigotine, a dopamine agonist in development, has also been shown to be efficacious. The greater proclivity for dopamine agonists to cause psychotoxicity has, however, limited their routine use in the elderly. Selective monoamine oxidase type B (MAO-B) inhibitors, used as monotherapy, delay the need for the introduction of levodopa by about 9 months. These agents appear to be less efficacious than dopamine agonists but are better tolerated. Concern has been expressed about the potential of the MAO-B inhibitor selegiline (deprenyl) to induce cardiovascular adverse effects (orthostatic hypotension), either directly or through its amphetamine catabolites. Rasagiline is a new MAO-B inhibitor that is not broken down to amphetamine derivatives and is indicated as both monotherapy in early PD and as adjunctive therapy in PD patients with motor fluctuations. Two older classes of agents have undergone a resurgence of interest in recent years. Amantadine, which enhances dopaminergic transmission and has antiglutamate activity, is occasionally used as monotherapy but has recently been widely used as an antidyskinetic agent in late-stage PD. Anticholinergic drugs, such as benztropine (benzatropine) and orphenadrine also provide control of symptoms when used as monotherapy, but their psychotoxic, cognitive and autonomic adverse events make them inappropriate for the treatment of the elderly. Effective therapy in PD should prevent disease progression and abolish motor and cognitive handicap. Currently, none of the existing drugs meets all these needs.
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PMID:Alternatives to levodopa in the initial treatment of early Parkinson's disease. 1615 77

An estimated 200,000 persons are hospitalized each year and 36,000 persons die from complications of influenza in the United States. The cornerstone of influenza prevention is annual vaccination. However, antiviral drugs are an important adjunct to vaccination for influenza prevention and control. Two classes of antiviral medications are available currently: adamantanes or M2 ion channel inhibitors (i.e., amantadine and rimantadine) and neuraminidase inhibitors (i.e., oseltamivir and zanamivir). The adamantanes are active against only influenza A viruses and are used for both treatment and chemoprophylaxis of influenza A, whereas the neuraminidase inhibitors are active against both influenza A and B viruses. Zanamivir is not approved for chemoprophylaxis of influenza in the United States. This report describes new findings regarding the resistance to adamantanes of influenza A viruses currently circulating in the United States and provides interim recommendations that these drugs not be used during the remainder of the 2005-06 influenza season. Amantadine also is used to treat symptoms of Parkinson disease and may continue to be used for this indication.
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PMID:High levels of adamantane resistance among influenza A (H3N2) viruses and interim guidelines for use of antiviral agents--United States, 2005-06 influenza season. 1642 59

In the treatment of Parkinson's disease, levodopa, DCI, MAO-B inhibitor, COMT inhibitors, dopamine receptor agonists, amantadine, anticholinergics have been applied and new drugs are being developed. Levodopa is still the golden standard in the treatment of Parkinson's disease. The study on levodopa bioavailability showed 3-4 times differences in individual patients. Drug-food interactions are prominent in levodopa. Low protein food increased levodopa bioavailability and improved no ON or delayed ON in the treatment of Parkinson's disease. Vitamine C or magnesium did not alter the bioavailability of levodopa. The bioavailability of levodopa between the levodopa/carbidioa (100/12.5) group and the levodopa/benserazide (100/25) group was studied in patients with Parkinson's disease by population PK study. C(max) of levodopa in levodeopa/benserazide group was twice as high as in levodopa/carbidopa group. Domperidone, a dopamine receptor antagonist applied as an antiemetic inceases vowel movement. The effect of domperidone on levodopa bioavailability was studied, and the combination of domperidone with levodopa increased AUC of levodopa. Clarythromycin or grape fruit juice inhibits both of CYP3A4 and P-glycoprotein which work on metabolism and absorption of drugs. Coadministration of clarythromycin with ergot alkaloids such as cabergoline or bromocriptine increased the AUC up to 2-3 times. Amantadine is excreted through kidney without being metabolized and renal function is the most important factor in the blood concentration of amantadine. In elder women with the body weight of 50 kg or less, creatinine clearance is less than 50 ml/min even though the serum creatinine is within the normal range. Selegiline is metabolized through CYP2D6 and 3A4. Coadministration of qunidine, cimetidine, maclorides, antifungals, grape fruit juice increase the bioavailability of selegiline and may augment the antiparkinsonian effect.
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PMID:[Inter- and intraindividual pharmacokinetic variations in the treatment of Parkinson's disease]. 1644 56

In the last several years, amantadine has been increasingly prescribed for akinesia in Parkinson's disease and to combat fatigue associated with multiple sclerosis. Amantadine is a well-known medication involved in drug-induced livedo reticularis (LR), yet remains under-reported in the English literature. We describe 2 patients with amantadine livedo reticularis: one patient with multiple sclerosis had, previous to this eruption, tolerated 4 years of amantadine therapy without adverse reactions and another patient with Parkinson's disease who developed LR 1 month after starting amantadine.
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PMID:Amantadine-induced livedo reticularis: a report of two cases. 1657 66

The objective of this study is to compare the occurrence of dementia among Parkinson's disease (PD) patients treated with amantadine (AM group) with those never exposed to it (NoAM group). PD dementia shares neuroanatomical and biochemical similarities with Alzheimer's disease (AD). Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist has been shown to be beneficial in AD. Memantine is a dimethyl derivative of amantadine, which also possesses NMDA receptor blocking properties. We hypothesized that amantadine could have a beneficial effect on the occurrence of PD dementia. PD patients attending the Movement Disorders Clinics in Hillel Yaffe, Asaf Harofe Medical Centers (Israel) and Pisa (Italy) were included. Taking the onset of dementia as the endpoint, survival curves for AM and NoAM patients were estimated by the Kaplan-Meier method. The study population consisted of 593 patients (age, 69.5 +/- 9.9 years; PD duration, 9.2 +/- 6.0 years; 263 patients (44%) amantadine treated). The endpoint of dementia was reached by 116 patients (20%). PD duration until dementia was significantly longer for AM patients (9.1 +/- 5.7 years) than for NoAM patients (5.9 +/- 4.6 years, P = 0.006). The duration of amantadine exposure positively correlated with PD duration until dementia (P = 0.0001). Survival analysis, taking dementia onset as endpoint, showed slower mental decline in AM patients (Log rank P = 0.0049, Wilcoxon P = 0.0024). Mini-Mental State Examination scores were significantly higher for AM patients than for the NoAM group (P = 0.01). Age of PD onset also significantly influenced the duration of PD until dementia. Amantadine use may delay the onset of dementia in PD patients and may attenuate its severity.
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PMID:Association between amantadine and the onset of dementia in Parkinson's disease. 1711 64

Amantadine-sulfate has been used for several decades to treat acute influenza A, Parkinson's disease (PD), and acute or chronic drug-induced dyskinesia. Several mechanisms of actions detected in vivo/in vitro including N-methyl-D-aspartate (NMDA)-receptor antagonism, blockage of potassium channels, dopamine receptor agonism, enhancement of noradrenergic release, and anticholinergic effects have been described. We used transcranial magnetic stimulation (TMS) to evaluate the effect of single doses of amantadine on human motor cortex excitability in normal subjects. Using a double-blind, placebo-controlled, crossover study design, motor thresholds, recruitment curves, cortical stimulation-induced silent period (CSP), short intracortical inhibition (ICI), intracortical facilitation (ICF), and late inhibition (L-ICI) in 14 healthy subjects were investigated after oral doses of 50 and 100 mg amantadine with single and paired pulse TMS paradigms. Spinal cord excitability was investigated by distal latencies and M-amplitudes of the abductor digiti minimi muscle. After intake of amantadine, a significant dose-dependent decrease of ICF was noticed as well as a significant increase of L-ICI as compared to placebo. The effect on ICF and L-ICI significantly correlated with amantadine serum levels. ICI was slightly increased after amantadine intake, but the effect failed to be significant. Furthermore, amantadine had no significant effects on motor thresholds, MEP recruitment curves, CSP, or peripheral excitability. In conclusion, a low dose of amantadine is sufficient in modulating human motor cortex excitability. The decrease of ICF and increase of L-ICI may reflect glutamatergic modulation or a polysynaptic interaction of glutamatergic and GABA-ergic circuits. Although amantadine has several mechanisms of action, the NMDA-receptor antagonism seems to be the most relevant effect on cortical excitability. As L-ICI can be influenced by this type of drug, it may be an interesting parameter for studies of motor learning and use-dependent plasticity.
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PMID:Modulation of human motor cortex excitability by single doses of amantadine. 1679 70

Investigation of the pathophysiology of psychosis in Parkinson's disease (PD), as well as the assessment of potential novel therapeutics, has been limited by the lack of a well-validated animal model. MPTP-lesioned primates exhibit abnormal behaviors that are distinct from dyskinesia and parkinsonism and may represent behavioral correlates of neural processes related to psychosis in PD. Here we assess four types of behavior--agitation, hallucinatory-like responses to nonapparent stimuli, obsessive grooming, and stereotypies that are termed "psychosis-like"--and define their pharmacology using a psychosis-like behavior rating scale. By assessing the actions of drugs known to enhance or attenuate psychosis in PD patients, we find that the pharmacology of these behaviors recapitulates, in several respects, the pharmacology of psychosis in PD. Thus, levodopa and apomorphine elicited psychosis-like behaviors. Amantadine significantly decreased levodopa-induced dyskinesia but exacerbated psychosis-like behaviors. Haloperidol reduced psychosis-like behaviors but at the expense of increased parkinsonian disability while the atypical neuroleptics clozapine and quetiapine reduced psychosis-like behaviors without significant effect on parkinsonian disability. The response of different components of the psychotomimetic behavior suggested the involvement of both dopaminergic and nondopaminergic mechanisms in their expression.
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PMID:Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson's disease. 1696 Aug 62

Data from a survey of 6,620 Parkinson's disease patients were examined for correlation of freezing with age, sex, duration, subjective severity of Parkinson's disease, and antiparkinsonian medication. Forty-seven percent of the patients reported experiencing freezing regularly. Logistic regression analysis showed that freezing was significantly associated with a longer disease duration and a more advanced stage of the disease. Freezing episodes were more likely in men than in women and in patients taking, in addition to levodopa, Entacapone, Amantadine, or dopamine agonists. Finally, patients considering tremor as their main symptom reported freezing less frequently. Common antiparkinsonian drugs given in combination with levodopa were not negatively correlated with freezing. The results underline the necessity to develop appropriate countermeasures against this phenomenon, which is widely known to cause significant impairment of patients' quality of life and - as our data also showed - may cause traffic accidents in licensed patients.
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PMID:Predictors of freezing in Parkinson's disease: a survey of 6,620 patients. 1737 27

A 61-year-old man with Parkinson's disease (PD) developed sudden-onset visual impairment after initiation of amantadine treatment. Ophthalmologic examination revealed corneal endothelial edema. Discontinuation of amantadine resulted in rapid improvement of visual acuity. A review of the literature indicated only a few reports of amantadine-associated corneal dysfunction in patients with neurological disorders as well as influenza syndrome, but none with PD. Amantadine-associated visual impairment in PD could be possibly overlooked, since PD mainly affects elderly people who often develop aging-related ocular changes. The present report alerts neurologists and physicians in general to the peculiar ophthalmologic side effect of amantadine.
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PMID:Visual impairment in Parkinson's disease treated with amantadine: case report and review of the literature. 1750 24


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