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)

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

The purpose of this article is to provide an overview of some of the important information related to safety and tolerability of duloxetine. Duloxetine, a potent reuptake inhibitor of serotonin and noradrenaline, is effective for the treatment of major depressive disorder, anxiety disorder, and painful diabetic neuropathy (PDN). Duloxetine is safe and well-tolerated across indications, with few reported serious side effects. Common adverse events are consistent with the pharmacology of the molecule and are mainly referable to the gastrointestinal and the nervous systems. Duloxetine should not be used in combination with CYP 1A2 inhibitors or nonselective, irreversible monoamine oxidase inhibitors. Duloxetine has a generally favorable side effect profile and dosing is simple. Nausea is the most common side effect, but it occurs less frequently if treatment is initiated at 30 mg . day-1 and titrated after one week to 60 mg . day-1, an efficacious dosage at which pain relief can occur within one week. Clinical trials have demonstrated the analgesic efficacy of duloxetine for PDN and fibromyalgia in addition to improvements in quality-of-life measurements. Furthermore trials for osteoarthritis, headache, and the pain associated with Parkinson disease may provide insight into alternative uses for duloxetine.
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PMID:[Duloxetine for chronic pain management: pharmacology and clinical use]. 2390 4

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

Chronic pain is the most common non-motor symptom of Parkinson's disease (PD) and is often overlooked. Unilateral 6-hydroxydopamine (6-OHDA) medial forebrain bundle lesioned rats used as models for PD exhibit decreased sensory thresholds in the left hindpaw. Subthalamic deep brain stimulation (STN DBS) increases mechanical thresholds and offers improvements with chronic pain in PD patients. However, individual responses to STN high frequency stimulation (HFS) in parkinsonian rats vary with 58% showing over 100% improvement, 25% showing 30-55% improvement, and 17% showing no improvement. Here we augment STN DBS by supplementing with a serotonin-norepinephrine reuptake inhibitor commonly prescribed for pain, duloxetine. Duloxetine was administered intraperitoneally (30mg/kg) in 15 parkinsonian rats unilaterally implanted with STN stimulating electrodes in the lesioned right hemisphere. Sensory thresholds were tested using von Frey, Randall-Selitto and hot-plate tests with or without duloxetine, and stimulation to the STN at HFS (150Hz), low frequency (LFS, 50Hz), or off stimulation. With HFS or LFS alone (left paw; p=0.016; p=0.024, respectively), animals exhibited a higher mechanical thresholds stable in the three days of testing, but not with duloxetine alone (left paw; p=0.183). Interestingly, the combination of duloxetine and HFS produced significantly higher mechanical thresholds than duloxetine alone (left paw, p=0.002), HFS alone (left paw, p=0.028), or baseline levels (left paw; p<0.001). These findings show that duloxetine paired with STN HFS increases mechanical thresholds in 6-OHDA-lesioned animals more than either treatment alone. It is possible that duloxetine augments STN DBS with a central and peripheral additive effect, though a synergistic mechanism has not been excluded.
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PMID:Effects of subthalamic deep brain stimulation with duloxetine on mechanical and thermal thresholds in 6OHDA lesioned rats. 2798 22


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