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)

Parkinson disease is characterized by selective degeneration of mesencephalic dopaminergic neurons, and endogenous dopamine may play a pivotal role in the degenerative processes. Using primary cultured mesencephalic neurons, we found that glutamate, an excitotoxin, caused selective dopaminergic neuronal death depending on endogenous dopamine content. Pramipexole, a dopamine D2/D3 receptor agonist used clinically in the treatment of Parkinson disease, did not affect glutamate-induced calcium influx but blocked dopaminergic neuronal death induced by glutamate. Pramipexole reduced dopamine content but did not change the levels of total or phosphorylated tyrosine hydroxylase, a rate-limiting enzyme in dopamine synthesis. The neuroprotective effect of pramipexole was independent of dopamine receptor stimulation because it was not abrogated by domperidone, a dopamine D2-type receptor antagonist. Moreover, both active S(-)- and inactive R(+)-enantiomers of pramipexole as a dopamine D2-like receptor agonist equally suppressed dopaminergic neuronal death. These results suggest that pramipexole protects dopaminergic neurons from glutamate neurotoxicity by the reduction of intracellular dopamine content, independently of dopamine D2-like receptor activation.
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PMID:Novel neuroprotective mechanisms of pramipexole, an anti-Parkinson drug, against endogenous dopamine-mediated excitotoxicity. 1716 93

The results of mirapex (pramipexol) treatment of 402 patients with Parkinson's disease and juvenile parkinsonism during the period from 6 months to 7 years are summarized. Mirapex was used in monotherapy as well as in combination with levadopa and other antiparkinsonic drugs. The drug was well tolerated and effective in rest tremor, hypokinesia, muscle rigidity and depression, the more pronounced effect being seen at the early stage of the disease. The use of mirapex allows an effective control of motor fluctuations developing during long-term continuous levodopa therapy. The results obtained characterize mirapex as a drug of choice in the treatment of juvenile parkinsonism. In case of a break in mirapex treatment, the recommencement of treatment usually is not accompanied by reduced sensitivity to drug effect.
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PMID:[7-year experience in usage of mirapex in patients with different forms of primary parkinsonism]. 1718 Jul 57

The blood-brain barrier (BBB) transport of pramipexole, a potent dopamine receptor agonist with high efficacy for Parkinson's disease, was mainly characterized using immortalized rat brain capillary endothelial cells (RBEC)1 as an in vitro BBB model. [(14)C]Pramipexole uptake by RBEC1 was dependent on temperature and pH, but not sodium ion concentration or membrane potential. The uptake was inhibited by several organic cations including pyrilamine. Mutual inhibition was observed between pramipexole and pyrilamine. In addition, [(14)C]pramipexole uptake was stimulated by preloading unlabeled pramipexole. RT-PCR analysis for organic cation transporters (rOCT1-3, rOCTN1-2) in RBEC1 was performed. The mRNA level of rOCTN2 was the highest, followed by rOCTN1, while expression of rOCT1, rOCT2 and rOCT3 was negligible. The brain uptake of [(14)C]pramipexole, which was measured by the in situ rat brain perfusion technique, was significantly inhibited by unlabeled pramipexole. These results suggest that pramipexole is, at least in part, transported across the BBB by an organic cation-sensitive transporter. The pramipexole transport in RBEC1 was pH-dependent, but sodium- and membrane potential-independent.
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PMID:Blood-brain barrier transport of pramipexole, a dopamine D2 agonist. 1730 2

We present a review of the literature on dopamine receptor agonists along with our own data on the treatment of Parkinson's disease (PD) with Mirapex, which was used in 30 patients (mean age 61.8 +/- 7.7 years, duration of disease 8.4 +/- 1.3 years). Mirapex was used at a dose of 3.5 +/- 1.1 mg/day on the background of treatment with levodopa preparations. The efficacy of Mirapex was assessed using quantitative scales. Improvements were demonstrated in general state, motor activity, daily activities, and the quality of life. Attention is drawn to a decrease in the severity of motor fluctuations and dyskinesias and in anxiety and depression, and to improvements in cognitive functions. The significance of the combination of the high efficacy and good tolerance of this agent is emphasized.
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PMID:Use of the dopamine receptor agonist Mirapex in the treatment of Parkinson's disease. 1765 23

We report a case of antecollis, or dropped head with Parkinson's disease (PD) induced by pramipexole, a nonergot dopamine agonist. An 80-year-old woman presented with progressively severe neck flexion, which developed within a few weeks of taking pramipexole at 3 mg/day. She had a disturbed gait and complained of difficulty in daily activity because of restricted visual field and severe stooped posture. Surface EMG showed disproportionate tonus of the neck muscles but needle EMG of the neck muscles was normal. Withdrawal of pramipexole resulted in immediate improvement; the patient could keep the head in natural position and walk normally. Pramipexole-induced antecollis may be serious, but is a reversible dystonia in patients with PD. Clinicians should be aware of such complication.
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PMID:Pramipexole-induced antecollis in Parkinson's disease. 1782 96

The number of dopamine agonists (DA) used in Parkinson's disease (PD) is gradually increasing. They have different affinity to the dopamine receptor subtypes. When choosing one of these drugs one should consider its efficacy in monotherapy in early phase and in combined therapy with levodopa in advanced PD, side effects profile, effectiveness in non-motor symptoms of PD, dosing and route of administration. The efficacy of new DA (pramipexol, ropinirol, cabergoline) is probably higher than bromocriptine and comparable to pergolide with similar profile of the most common side effects (headache, vertigo, nausea, somnolence, oedema). However, fibrosis of the pleura, peritoneum and pericardium as well as valvular heart disease (caused by noninflammatory fibrotic degeneration) are significantly more common after ergoline DA (pergolide, cabergoline). Pramipexol shows antidepressant activity. Ropinirol is metabolised by the liver and can be safely administered in renal insufficiency. Pramipexol is excreted in urine and the risk of interaction with other drugs metabolised in the liver is reduced. Rotigotine is the only DA available as skin patches. Whenever necessary, one DA agent can be changed safely overnight to another one.
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PMID:[Choosing a dopamine agonist in Parkinson's disease]. 1794 54

Pramipexole is a non-ergoline dopamine agonist with a high selectivity for D(2) and D(3) receptors. Initially approved for Parkinson's disease, it was approved by the FDA and EMEA in 2006 for the treatment of idiopathic restless legs syndrome in adults. A single oral dose of pramipexole of between 0.125 and 0.750 mg, taken 2 - 3 h before bedtime, is usually able to control sensory symptoms and motor signs of restless legs syndrome. In clinical practice, tailoring pramipexole treatment based on demographic and clinical characteristics of patients is recommended. In addition, pramipexole seems to be safe and well tolerated. Augmentation, the most common side effect of levodopa, is less prevalent after treatment with pramipexole. In addition, the recurrence of unpleasant symptoms due to pramipexole is uncommon.
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PMID:Clinical experience with pramipexole in the treatment of restless legs syndrome. 1824 14

Recent case-series studies indicated that a medication used to treat Parkinson's disease (PD), in particular Pramipexole, is associated with gambling. A case-series study cannot test this hypothesis; therefore, we need to design a case-control or cohort study to test the aforementioned hypothesis. Typical of a case-control design, we sampled on the dependent variable, which we defined as incident gambling in PD. A research neurologist, who was kept uninformed of the case-control status, retrospectively measured the exposure of interest (i.e. medications used to treat PD) by using the medical database system of Mayo Clinic Jacksonville. Eleven patients with PD without history of gambling, but had newly developed gambling, were matched by age and sex to the control group of 37 PD patients without gambling at a ratio of one case to at least three controls. Disease duration, age, and sex did not differ between cases and controls. Combined therapy with Pramipexole and levodopa did not increase the risk of gambling as compared to monotherapy with Pramipexole (OR, 0.15; 95% CI, 0.01-1.26). Treatment with Pramipexole was associated with increased risk of gambling and this association approached significance (OR, 3.6; 95% CI, 0.9-14.9). Patients with PD who newly developed gambling behavior were more likely to have been taking Pramipexole than other anti-PD medication. However, the association between Pramipexole and gambling behavior is not necessarily etiologic.
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PMID:Medications used to treat Parkinson's disease and the risk of gambling. 1831 5

Dopamine agonists are established as effective drugs for the symptomatic treatment of Parkinson's disease (PD) throughout its course. As monotherapy, they produce effective control of motor symptoms and combine this with a low risk for motor complications. As an adjunct to levodopa, they improve motor control and limit the need for levodopa in those patients in whom this may be considered relevant. The non-ergot dopamine agonists in particular have a good safety profile, although as with other agonists, sedation, and cognitive and behavioral problems may be limiting in some patients. Pramipexole has shown benefit in improving depressive symptoms in PD. Ropinirole and pramipexole have both demonstrated a reduction in the rate of loss of nigrostriatal innervation as determined by imaging in PD patients, when compared with levodopa. Thus, dopamine agonists contribute to several dimensions of the management of PD and have become an integral part of the disease treatment algorithm.
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PMID:Dopamine agonists in Parkinson's disease. 1841 67

Pramipexole, a dopamine D2/D3 receptor agonist used in the treatment of Parkinson's disease, has been reported to have neuroprotective potential. We investigated the effect of pramipexole against cell death induced by a proteasome inhibitor, lactacystin, using primary mecencephalic neuronal cultures and SH-SY5Y cells. In E14 rat primary mesencephalic cultures, the number of surviving tyrosine hydroxylase (TH)-positive neurons and microtubule associated protein 2 (MAP2)-positive neurons was decreased by exposure to 1-5 microM lactacystin in a dose-dependent manner. Pretreatment with 100 microM pramipexole rescued TH-positive neurons and MAP2-positive neurons from the toxicity of lactacystin. The protective effect of pramipexole was not selective for TH-positive dopaminergic neurons. However, the treatment with 100 microM pramipexole did not protect SH-SY5Y cells against lactacystin-induced cell toxicity and proteasome dysfunction. We hypothesized that the protective effect of pramipexole against the lactacystin-toxicity was not direct but a secondary effect mediated by astrocytes. Therefore, we investigated the efficacy of conditioned medium collected from mecencephalic astrocytes treated with pramipexole. The conditioned medium increased the viability of SH-SY5Y cells against the toxicity of lactacystin. Pramipexole increased the levels of brain derived neurotrophic factor (BDNF) in the conditioned medium of astrocyte cultures. These protective effects were not significantly inhibited by dopamine D2 or D3 receptor antagonists. We demonstrated that pramipexole had the protective effect against lactacystin toxicity, mediated by a neurotrophic effect of astrocyte-produced factors including BDNF.
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PMID:Pramipexole has astrocyte-mediated neuroprotective effects against lactacystin toxicity. 1855 4


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