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)

Apomorphine, a non-ergot derivative, is a potent, directly acting dopamine receptor agonist with high affinity to D4, lower to D2, D3, D5, the lowest to D1-like dopamine receptors as well as to serotonin and adrenoreceptors. Subcutaneous apomorphine is currently used in Parkinson's disease as an add-on to levodopa therapy or monotherapy for management of sudden, unexpected and refractory to levodopa-induced off state and fluctuation in advanced stage of illness. Many clinical trials have shown markedly (about 50-72%) reduced time of off phases. Other indications include the challenge test for determining the dopaminergic responsiveness. Apomorphine is used subcutaneously either as intermittent rescue injections or continuous infusions. Several other routes - transdermal, sublingual, intranasal, rectal and intravenous infusion - have been tried. Oral administration is not recommended. Apomorphine has rapid onset of antiparkinsonian action, qualitatively comparable to that of levodopa, short duration of action and stable efficacy with usually mild adverse events similar to other dopamine agonists. Domperidone or trimethobenzamide should be introduced before starting apomorphine treatment to reduce occurrence of peripheral adverse events (nausea, vomiting, orthostatic hypotension). Dyskinesias, sleep disturbances, hallucinations, delusion, oedema and yawning can occur, but some side effects are connected only with a specific route (for example skin nodules appearing during subcutaneous administration). Despite its long history, apomorphine is registered and used in only a few countries. Apomorphine warrants wider application in treatment of advanced Parkinson disease but the high cost of the drug, the necessity of concomitant treatment for prevention of side effects and subcutaneous administration restrict its use.
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PMID:[Apomorphine in off state--clinical experience]. 1794 58

Domperidone, a dopamine antagonist that does not easily cross the blood-brain barrier, is considered the gold standard for treating gastrointestinal symptoms in patients with Parkinson's disease (PD) because the risk of developing extrapyramidal adverse effects is considered minimal. On the other hand, cardiotoxicity related to domperidone is not a new issue. In fact, arrhythmias, sudden death and cardiac arrest were reported with high intravenous doses in the 80s. Concern about the cardiotoxicity of oral domperidone has arisen more recently after the publication of two case-control studies which have questioned domperidone's safety even further, especially in patients > 60 years and in doses >30 mg/day. Very little is known about domperidone's cardiac effects in patients with PD. In addtion, pharmacoepidemiological data about specific antiemetic use in these patients is scarce, with almost anecdotal reports of inappropriate centrally acting antidopaminergic drugs like metoclopramide in the hospital setting. As a result, and even no cases of serious arrhythmias or sudden cardiac death associated with domperidone concerning patients with PD have been reported, no definitive conclusions can be drawn about its safety. In conclusion, despite domperidone is still recognized as the first choice for treating gastrointestinal symptoms PD, doses above 30 mg/daily should only be considered with special caution taking into account its potential cardiotoxic effects.
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PMID:Domperidone in Parkinson's disease: a perilous arrhythmogenic or the gold standard? 2365 49

Domperidone is an anti-dopaminergic drug used for the treatment of nausea, vomiting and dyspepsia. It has also been used in Parkinson's disease. In this study, five different brands of Domeperidone tablets were selected from the local market for evaluation of their quality as the local market is occupied of many competitors for a single generic. The evaluation of Domperidone tablets was done using various pharmacopoeial and non-pharmacopoeial tests. All the test results fell within BP specified limits for all the selected brands i.e. the results for Brands A to E for weight variation, thickness and diameter were satisfactory and within limits. For Brands A to E, the results for hardness and friability were also satisfactory i.e. 4-10kg/cm2and 0.1-0.6% respectively. The results for Brands A to E for disintegration were 2-6 minutes; for dissolution and assay, the results were 89-92% and 95-99% respectively. The results of similarity factor (f2) also showed that all brands of Domperidone have comparative dissolution profiles.
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PMID:Evaluation and comparison of different brands of domperidone tablets available in Karachi, Pakistan. 2501 63

Modified non-motor brainstem ventilatory control might be involved in Parkinson's disease. Our study was designed to investigate the impact of degeneration of the nigrostriatal dopaminergic pathway on resting breathing and hypoxic ventilatory response in conscious rats. The role of central and peripheral dopamine D2 receptors in the modulation of the hypoxic ventilatory response in conditions of dopamine shortage was examined. Adult Wistar rats received a unilateral double 6-hydroxydopamine lesion of the right medial forebrain bundle. After surgery, animals were placed in whole-body plethysmographic chamber and exposed to hypoxia (8% O2). One group of animals received inraperitoneal injections of either haloperidol or domperidone before hypoxia. Levels of dopamine and its metabolite in the brainstem and striatum were assessed. Neurotoxin treatment evoked limb use asymmetry. No effect on the resting normoxic respiration was observed. An increase in tidal volume and a decrease in respiratory rate during respiratory response to hypoxia with short magnification of minute ventilation were predominant effects. Domperidone treatment in intact animals evoked a significant increase in normoxic tidal volume, while haloperidol potentiated tidal volume increase in response to hypoxia. After the lesion, the effects of both antagonists were absent. In rats with Parkinson's, the content of dopamine and its metabolite decreased substantially in the injured striatum. Augmentation of a tidal volume response to hypoxia, and the absence of stimulatory effect of intraperitoneal domperidone on normoxic and haloperidol on hypoxic tidal volume, in lesioned rats indicated altered control of breathing. This could be the result of a dopamine deficiency in the striatum and an increased turnover of DOPAC/DA in the brainstem.
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PMID:Hypoxic ventilatory response after dopamine D2 receptor blockade in unilateral rat model of Parkinson's disease. 2670 38


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