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)

(1) The restless legs syndrome consists of unpleasant sensory and motor symptoms of varying intensity in the lower limbs. Symptoms occur at rest, seated or lying down, are more intense in the evening and at night, and are relieved by moving the limb. This syndrome does not cause serious physical complications. When sleep disturbances occur, non drug methods should be tried first. (2) Ropinirole is a dopaminergic agonist initially marketed for the treatment of Parkinson's disease. It is the first drug to be approved for restless legs syndrome in France. (3) Three double-blind randomised placebo-controlled trials with similar designs showed minimal differences on a composite rating scale. After 12 weeks of treatment, ropinirole led to an improvement of about 3 points on a 40-point scale compared with placebo. (4) A 12-week double-blind randomised controlled trial and including patients who had "responded" to ropinirole showed a lower relapse rate in the group that continued to use ropinirole (32.6%) instead of switching to placebo (57.8%). However, we do not know if this was because of continued drug efficacy or a rebound effect in the placebo group. (5) The adverse effects of ropinirole in patients with restless legs syndrome had already been observed in the treatment of Parkinson's disease, and included nausea, vomiting, drowsiness, a sudden urge to sleep, syncope, hypotension, and hallucinations. (6) An increase in the severity of restless legs symptoms, typically seen with levodopa, was not evaluated in clinical trials of ropinirole. Some cases have nevertheless been reported. They describe the appearance of symptoms increasingly early in the evening, then in the afternoon, or as a rebound effect in the morning or the latter part of the night. Their intensity increases and can affect other parts of the body. (7) In practice, ropinirole has a negative risk-benefit balance in restless legs syndrome, which is a minor health disorder.
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PMID:Ropinirole: new indication. Restless legs: disproportionate adverse effects. 1712 23

Ropinirole is a non-ergoline selective D2 dopamine agonist. Its efficacy and safety has been established in several controlled double-blind studies in patients with early and advanced Parkinson's disease. It is assumed that the improvement in the activities of daily living under ropinirole is not only due to the improved motor symptoms but also due to the improvement of non-motor symptoms like symptoms of mood and anxiety. The objective of this post marketing surveillance study was to show that under the conditions of the daily routine in the neurologic practice ropinirole may not only improve motor symptoms, the activity of daily living and complications of the treatment (dystonia, dyskinesia) but also alleviate symptoms of depression and anxiety. A total of 110 neurological practices enrolled 327 patients in early and advanced stages of the disease (139 females, 188-males; mean age: 67 years). They were treated with ropinirole as monotherapy and as adjunctive therapy with l-dopa over a period of 12 - 14 weeks. Selected symptoms of the Unified Parkinson's Disease Rating Scale (UPDRS) part II-IV and symptoms of depression and anxiety were rated by the clinicians. Mood and functional impairment in job, family and social life were rated by the patients using selected items of the Beck Depression Inventory and the Sheehan Disability Scale (SDS). The different subtypes, i. e. the akinetic-rigid, tremor-dominant and the mixed subtype, are described separately. The total UPDRS score at baseline was similar for all three subtypes and there was also a similar improvement in the three groups under ropinirole. Both according to self-rating and to clinician rating the symptoms of depression and anxiety at baseline were more severe in the akinetic-rigid and the mixed subtype compared to the tremor-dominant subtype. The symptoms considerably improved and were reduced by 48 % under therapy with ropinirole. Adverse events were reported by 7.7 % of the patients. The surveillance study has shown that ropinirole may improve not only motor symptoms, activities of daily living and complications of treatment but also symptoms of mood and anxiety.
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PMID:[Improvements in motor and non-motor symptoms in parkinson patients under ropinirole therapy]. 1742 44

Ropinirole, which is a non-ergot dopamine agonist derivative, exerts therapeutic benefits in Parkinson's disease (PD). Based on recent studies implicating dopamine receptors 2 and 3 (D2R and D3R) as possible targets of ropinirole, we over-expressed these dopamine receptor genes in the dopamine-denervated striatum of rodents to reveal whether their over-expression modulated ropinirole activity. Adult Sprague-Dawley rats initially received unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. At 1 month after surgery, successfully lesioned animals (3 or less forelimb akinesia score, and 8 or more apomorphine-induced rotations/min over 1 h) were randomly assigned to intrastriatal injection (ipsilateral to the lesion) of blank lentiviral vector, D2R, D3R or both genes. At about 5 months post-lesion, ropinirole (0.2 mg/kg, i.p.) was administered daily for 9 consecutive days. The subtherapeutic dose of ropinirole improved the use of previously akinetic forelimb and produced robust circling behavior in lesioned animals with striatal over-expression of both D2R and D3R compared to lesioned animals that received blank vector. In contrast, the subtherapeutic dose of ropinirole generated only modest motor effects in lesioned animals with sole over-expression of D2R or D3R. Western immunoblot and autoradiographic assays showed enhanced D2R and D3R protein levels coupled with normalized D2R and D3R binding in the ventral striatum of lesioned animals with lentiviral over-expression of both D2R and D3R relative to vehicle-treated lesioned animals. Immunohistochemical analyses showed that D2R and D3R GFP fluorescent cells colocalized with enkephalin and substance P immunoreactive medium spiny neurons. These data support the use of the subtherapeutic dose of ropinirole in a chronic model of PD.
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PMID:Overexpression of D2/D3 receptors increases efficacy of ropinirole in chronically 6-OHDA-lesioned Parkinsonian rats. 1757 46

Neuroprotection in Parkinson's disease is defined as halting or slowing of the progression of neurodegeneration. Neuroprotective properties of dopamine agonists may be mediated via several mechanisms, (levodopa-sparing effect, decreased dopamine turnover, antioxidant activity or inhibition of the subthalamic nucleus). Many preclinical studies demonstrate that bromocriptine, pergolide, pramipexole, ropinirole and other dopamine agonists provide significant protection against neuronal loss in experimental models. Only a few studies have investigated the potential neuroprotective effect of dopamine agonists at the clinical level. Several recent trials have used neuroimaging biomarkers to assess the rate of dopamine neuron loss in dopamine agonist-treated versus levodopa-treated patients using fluoro-dopa PET or beta-CIT SPECT. Ropinirole slowed the decline of putaminal dopamine storage capacity and pramipexole reduced decline in striatal beta-CIT uptake to a similar extent, compared to levodopa. It is not possible to exclude, however, some pharmacologic or pharmacodynamic effects of drugs on imaging markers in these studies, as well as symptomatic effects of dopamine agonist treatment in clinical outcomes.
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PMID:[Neuroprotective effect of dopamine agonists]. 1794 55

Ropinirole, a D2/D3 receptor agonist has been reported to have neuroprotective effects. We showed that ropinirole can prevent rotenone-induced apoptosis in dopaminergic cell line SH-SY5Y through D3 receptor. We found that ropinirole can block the rotenone-induced phosphorylation of JNK, P38 and p-c-Jun, but promote the phosphorylation of ERK1/2. Furthermore, we demonstrated that ropinirole can reduce the rotenone-induced cleavages of caspase 9, caspase 3 and PARP and elevate the expression of anti-apoptotic proteins of p-Akt and bcl-2. These results provide a basis for neuroprotection by this drug for the treatment of Parkinson disease.
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PMID:D2/D3 receptor agonist ropinirole protects dopaminergic cell line against rotenone-induced apoptosis through inhibition of caspase- and JNK-dependent pathways. 1824 71

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

Clinical evidence suggests that stimulation of the D(1) rather than D(2) dopamine receptor is related to the development of dyskinesias in Parkinson's disease (PD). We evaluated, in the 6-hydroxydopamine rat model of PD, sensitization of contralateral turning (SCT) behaviour and abnormal involuntary movements (AIMs) as behavioural parameters of dyskinetic response, and changes in zif-268 mRNA expression in striatonigral and striatopallidal neurons on subchronic administration of the D(2)/D(3) agonist ropinirole, defined as a mild dyskinetic drug in the clinic. Results were compared with previous findings on repeated L-dopa treatment. Ropinirole displayed a mild dyskinetic response characterized by SCT only, which contrasted with the presence of SCT in association with AIMs elicited by repeated L-dopa. Zif-268 mRNA levels were decreased in both striatonigral and striatopallidal neurons by ropinirole, in contrast to hyper-expression of zif-268 mRNA selectively induced by L-dopa in striatonigral neurons. Unbalanced responsiveness of striatal efferent neurons might represent a molecular correlate of high dyskinetic potential and AIMs in rats; in contrast, a balanced striatal output might underlie the low dyskinetic potential displayed by ropinirole.
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PMID:Direct and indirect striatal efferent pathways are differentially influenced by low and high dyskinetic drugs: behavioural and biochemical evidence. 1858 75

Ropinirole is a non-ergolinic dopamine agonist, which has been used for over 10 years for the treatment of Parkinson's disease. A new formulation (PR = prolonged release) has been developed, which allows the drug to be released slowly (continuously) so that it only has to be given once daily. Switching from the previous ropinirole immediate release ( ropinirole IR) to the prolonged release (ropinirole PR) formulation at the nearest equivalent total daily dose, can take place overnight and the acceptance and tolerability are good. The advantages are once-daily dosing, faster titration with good tolerability and more stable plasma levels. The new formulation is regarded as valuable addition to the currently available medications.
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PMID:Initial experience with ropinirole PR (prolonged release). 1878 84

Ropinirole prolonged release is a non-ergoline dopamine receptor agonist that is indicated for the treatment of Parkinson's disease. * Once-daily ropinirole prolonged release and three-times-daily ropinirole immediate release have similar exposure over 24 hours. The prolonged-release formulation is associated with fewer fluctuations in plasma ropinirole concentrations. * Two well designed, placebo- or active comparator-controlled trials examined the efficacy of ropinirole prolonged release in patients with advanced Parkinson's disease suboptimally controlled by levodopa. In the placebo-controlled trial, 24 weeks' therapy with ropinirole prolonged release 6-24 mg once daily reduced hours of 'off' time (primary endpoint) to a significantly greater extent than placebo. In the active comparator-controlled trial, significantly more ropinirole prolonged-release recipients than ropinirole immediate-release recipients maintained a >or=20% reduction from baseline in 'off' time at week 24 (primary endpoint). *Ropinirole prolonged release 6-24 mg once daily was generally well tolerated in patients with advanced Parkinson's disease; adverse events were generally typical of non-ergoline dopamine receptor agonists.
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PMID:Ropinirole prolonged release: in advanced Parkinson's disease. 1906 77

Ropinirole prolonged release is a once-daily, 24-hour formulation of ropinirole, a non-ergot dopamine agonist. It is approved as monotherapy and as an adjunct to levodopa in the treatment of Parkinson's disease (PD). Several potential advantages of ropinirole prolonged release compared to the immediate release formulation include maintaining more consistent dopaminergic activity with steadier plasma levels, increased tolerability, greater compliance from a simpler once-daily dosing regimen and ease in dose titration. In a randomized, double-blind, non-inferiority, crossover study, ropinirole prolonged release was shown to have comparable efficacy and tolerability to immediate release ropinirole in early PD patients, with significantly greater compliance. Subjects were converted overnight between ropinirole formulations without loss of efficacy and with good tolerability. In a randomized, double-blind, placebo-controlled study in advanced PD, daily "off" time was reduced by an average of 2.1 hours with ropinirole prolonged release compared to 0.4 hours with placebo. Patients on ropinirole prolonged release were also more likely to require less daily levodopa. Ropinirole prolonged release is well tolerated with a similar adverse effect profile to other non-ergot dopamine agonists. The most common adverse effects include dyskinesia, nausea, dizziness, hallucinations, somnolence, abdominal pain or discomfort and orthostatic hypotension. Ropinirole prolonged release is a safe and effective treatment option for both early and advanced PD. This manuscript briefly reviews the current pharmacological treatment options for PD and provides a more detailed review of the currently available data regarding ropinirole prolonged release as a treatment option for PD.
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PMID:A review of ropinirole prolonged release in Parkinson's disease. 1950 79


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