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)

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

Pramipexole is a non-ergot dopamine agonist shown to be efficacious in the treatment of Parkinson's disease (PD). This review addresses the literature concerning pramipexole's efficacy in treating motor and non-motor symptoms in PD, its impact on the development of dyskinesias and response fluctuations, the issue of neuroprotection, and the risk for developing adverse events such as increased somnolence, attacks of sudden onset of sleep, cardiac valvulopathy and impulse control disturbances.
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PMID:Update on the use of pramipexole in the treatment of Parkinson's disease. 1872 40

More therapeutic options have become available for Parkinson's disease (PD) in recent years, leading to significant improvements in motor control both at early and advanced disease stages. More importantly, the need to expand disease management beyond motor symptom control has been recently highlighted and contribution of non-motor features to quality of life is now relevant. Dopamine agonists represent a valid therapeutic option in PD and their effect on non-motor domains like mood or cognition is now acknowledged as a key factor in fully addressing patients' needs. Pramipexole is a well established dopamine agonist that is currently being investigated for its potential disease-modifying effect and action on mood in PD. In this review we will examine factors contributing to treatment decision-making and discuss how a proper balance between motor and non-motor features should be aimed for in approaching PD therapy.
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PMID:Dopamine agonist-based strategies in the treatment of Parkinson's disease. 1938 65

Restless legs syndrome (RLS) is characterized by paraesthesias-dysesthesias and motor restlessness worsening at rest-in the evening, with at least temporary relief by activity. Its etiology is unknown, though it could be secondary to various conditions. It is well known, however, that dopamine plays a crucial role in the pathophysiology of RLS, as dopaminergic agonists achieve marked improvement. Pramipexole is a nonergoline compound with selectivity for D3 dopamine receptors. This drug is very effective in the treatment of idiopathic and secondary RLS and in treatment-resistant patients, as shown by double-blind, placebo-controlled studies in adults. In children, studies are much more limited, and RLS is often misdiagnosed as "growing pain" or attention deficit hyperactivity disorder. Pramipexole has been successful in open studies, eliminating clinical symptoms. This medication has the advantage of being free of the frequently encountered problems seen with ergot derivatives. The side-effects are limited, particularly at the dosages usually prescribed for RLS treatment: They are much lower than in Parkinson's disease, and inappropriate sleepiness and sleep attacks, particularly while driving, or compulsive behavior have not been seen. Compared with the adverse reactions of levodopa, including tolerance, rebound, and augmentation phenomena in RLS, which led to usage of dopamine agonists as first line of treatment for RLS, pramipexole has had one of the best profiles. Augmentation can still be noted with the drug, but after longer usage time compared with many other dopamine agonists. Although excessive daytime sleepiness has been noted, sleep attacks have not been encountered in RLS patients treated with pramipexole.
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PMID:Pramipexole: new use for an old drug - the potential use of pramipexole in the treatment of restless legs syndrome. 1941 89

Treatment with pramipexole, a dopamine D(3)/D(2) receptor agonist, reduces depressive symptoms in patients suffering from Parkinson's disease. To test the putative antidepressant quality of pramipexole, its effects were assessed in one of the most attractive animal models of depression, the olfactory bulbectomized (OBX) rat. Two experiments studied the effects of pramipexole on bulbectomy-induced hyperactivity. In experiment I, pramipexole was tested at 0.3 and 1.0 mg/kg together with the reference dopamine D(3) receptor agonist 7-OH-DPAT (0.1 mg/kg) and the tri-cyclic antidepressant imipramine (10 mg/kg). In experiment II, pramipexole was tested at lower doses: 0.03 and 0.1 mg/kg, with the same reference compounds. All animals were tested in the open field on days one (acute), seven (sub-chronic) and fourteen (chronic) of administration, as well as one week after cessation of treatment. Pramipexole, in a U-shaped dose response, reduced bulbectomy-induced hyperactivity after (sub) chronic but not acute administration (like imipramine and 7-OH-DPAT). The highest dose of pramipexole (1.0 mg/kg) did not reduce OBX hyperactivity during treatment. However, one week after cessation of treatment, all pramipexole (including the 1.0 mg/kg dose), 7-OH-DPAT and imipramine groups showed a reduction in OBX-induced hyperactivity. Pramipexole and 7-OH-DPAT exert an antidepressant profile in the OBX-rat model in normalizing bulbectomy-induced hyperactivity during (sub) chronic treatment. Moreover, treatment with both these compounds induced long-lasting changes in the bulbectomized brain similar to established antidepressants, strongly predicting antidepressant activity in major depression.
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PMID:Antidepressant effects of pramipexole, a dopamine D3/D2 receptor agonist, and 7-OH-DPAT, a dopamine D3 receptor agonist, in olfactory bulbectomized rats. 1954 14

Pramipexole, an agonist for dopamine (DA) D2/D3-receptors, has been used to treat both early and advanced Parkinson's disease (PD). In this study, we examined the effect of pramipexole on DA neurons in a PD model of C57BL/6 mice, which were treated with rotenone (30 mg/kg, p.o.) daily for 28 days. Pramipexole (1 mg/kg, i.p.) was injected daily 30 min before each oral administration of rotenone. Chronic oral administration of rotenone caused a loss of DA neurons in the substantia nigra pars compacta (SNpc), motor deficits and the up-regulation of alpha-synuclein immunoreactivity in some surviving DA neurons. Pramipexole inhibited rotenone-induced DA neuronal death and motor deficits, and reduced immunoreactivity for alpha-synuclein. In addition, pramipexole inhibited the in vitro oligomerization of human wild-type alpha-synuclein by H(2)O(2)plus cytochrome c. To examine the neuroprotective effect of pramipexole against oxidative stress, we used a DJ-1-knockdown SH-SY5Y cell line and electron spin resonance (ESR) spectrometry. Simultaneous treatment with H(2)O(2) and pramipexole resulted in the significant protection of DJ-1-knockdown cells against cell death in a concentration-dependent manner. A high concentration of pramipexole directly scavenged hydroxyl radical (*OH) generated from H(2)O(2) and Fe(2+). Furthermore, pramipexole increased Bcl-2 immunoreactivity in DA neurons in the SNpc. These results suggest that pramipexole may protect DA neurons against exposure to rotenone by chronic oral administration, and this effect is mediated by multiple functions including scavenging of *OH and induction of Bcl-2 protein.
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PMID:Neuroprotective effect of the antiparkinsonian drug pramipexole against nigrostriatal dopaminergic degeneration in rotenone-treated mice. 1964 76

The open 3-month study of influence of D2/D3 dopamine agonist pramipexole on of Parkinson's disease (PD) features, which are relatively resistant to traditional dopaminergic therapy: tremor, affective and cognitive impairment, has been conducted. Ninety-eight patients with PD, aged from 42 to 75 years (mean age 63,2+/-10,2 years), have been included in the study. Twenty percents of patients included were older than 70 years. The Hoehn and Yahr stage varied from 1 to 4 (men stage 2,5+/-0,8). Seventy percents of patients received levodopa (mean dosage 351,2+/-279,4 mg); 62% had motor fluctuations and 43% - dyskinesias. Pramipexole was titrated to effective dose (maximum 3 mg/d, mean 2,1 mg/d). The decrease of resting tremor by 50% and postural and kinetic tremor (assessed with the UPDRS and spiralography) by 37% was noticed to the end of 3 month. The severity of depressive symptoms measured with the Montgomery-Asberg scale and a modified version of the Geriatric Depression scale was reduced by one third. The statistically significant decrease of motor fluctuations and dyskinesias, increase of verbal fluency (but not other cognitive functions) were also found. The clinically significant effect of reducing of motor and non-motor symptoms was seen in 86% patients regardless of their age, illness duration, severity of motor deficit and affective and cognitive disturbances. The fair tolerability of the drug was shown including patients older than 70 years.
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PMID:[Influence of dopamine agonist pramipexole (mirapex) on tremor, cognitive and affective impairment in patients with Parkinson's disease]. 1973 67


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