The Experts below are selected from a list of 1065 Experts worldwide ranked by ideXlab platform
Mark Forrest Gordon - One of the best experts on this subject based on the ideXlab platform.
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ophthalmologic baseline characteristics and 2 year ophthalmologic safety profile of pramipexole ir compared with Ropinirole ir in patients with early parkinson s disease
Parkinson's Disease, 2016Co-Authors: William Seiple, Danna Jennings, Richard B Rosen, Leona Borchert, Lee Canale, Nora M Fagan, Mark Forrest GordonAbstract:Background. Parkinson’s disease (PD) progressively affects dopaminergic neurotransmission and may affect retinal dopaminergic functions and structures. Objective. This 2-year randomized, open-label, parallel-group, flexible-dose study, NCT00144300, evaluated ophthalmologic safety profiles of immediate-release (IR) pramipexole and Ropinirole in patients with early idiopathic PD with ≤6 months’ prior dopamine agonist exposure and without preexisting major eye disorders. Methods. Patients received labeled IR regimens of pramipexole () or Ropinirole () for 2 years. Comprehensive ophthalmologic assessments (COA) included corrected acuity, Roth 28-color test, slit-lamp biomicroscopy, intraocular pressure, computerized visual field test, fundus photography, and electroretinography. Results. At baseline, we observed retinal pigmentary epithelium (RPE) hypopigmentation not previously reported in PD patients. The estimated relative risk of 2-year COA worsening with pramipexole versus Ropinirole was 1.07 (95% CI: 0.71–1.60). Mean changes from baseline in Unified Parkinson’s Disease Rating System parts II
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Ophthalmologic Baseline Characteristics and 2-Year Ophthalmologic Safety Profile of Pramipexole IR Compared with Ropinirole IR in Patients with Early Parkinson’s Disease
Hindawi Limited, 2016Co-Authors: William Seiple, Danna Jennings, Richard B Rosen, Leona Borchert, Lee Canale, Nora Fagan, Mark Forrest GordonAbstract:Background. Parkinson’s disease (PD) progressively affects dopaminergic neurotransmission and may affect retinal dopaminergic functions and structures. Objective. This 2-year randomized, open-label, parallel-group, flexible-dose study, NCT00144300, evaluated ophthalmologic safety profiles of immediate-release (IR) pramipexole and Ropinirole in patients with early idiopathic PD with ≤6 months’ prior dopamine agonist exposure and without preexisting major eye disorders. Methods. Patients received labeled IR regimens of pramipexole (n=121) or Ropinirole (n=125) for 2 years. Comprehensive ophthalmologic assessments (COA) included corrected acuity, Roth 28-color test, slit-lamp biomicroscopy, intraocular pressure, computerized visual field test, fundus photography, and electroretinography. Results. At baseline, we observed retinal pigmentary epithelium (RPE) hypopigmentation not previously reported in PD patients. The estimated relative risk of 2-year COA worsening with pramipexole versus Ropinirole was 1.07 (95% CI: 0.71–1.60). Mean changes from baseline in Unified Parkinson’s Disease Rating System parts II+III total scores (pramipexole: 1 year, −4.1±8.9, and 2 years, −0.7±10.1, and Ropinirole: 1 year, −3.7±8.2, and 2 years, −1.7±10.5) and Hoehn–Yahr stage distribution showed therapeutic effects on PD symptoms. Safety profiles were consistent with labeling. Conclusions. The risk of retinal deterioration did not differ in early idiopathic PD patients receiving pramipexole versus Ropinirole. RPE hypopigmentation at baseline was not previously reported in this population. This trial is registered with NCT00144300
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falling asleep at the wheel motor vehicle mishaps in persons taking pramipexole and Ropinirole
Neurology, 1999Co-Authors: Steven J Frucht, Mark Forrest Gordon, J D Rogers, Paul Greene, Stanley FahnAbstract:The authors report a new side effect of the dopamine agonists pramipexole and Ropinirole: sudden irresistible attacks of sleep. Eight PD patients taking pramipexole and one taking Ropinirole fell asleep while driving, causing accidents. Five experienced no warning before falling asleep. The attacks ceased when the drugs were stopped. Neurologists who prescribe these drugs and patients who take them should be aware of this possible side effect.
Amos D Korczyn - One of the best experts on this subject based on the ideXlab platform.
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rotigotine transdermal patch in early parkinson s disease a randomized double blind controlled study versus placebo and Ropinirole
Movement Disorders, 2007Co-Authors: Nir Giladi, Babak Boroojerdi, Amos D Korczyn, David J Burn, Carl E Clarke, Anthony H V SchapiraAbstract:Rotigotine is a new, non-ergot dopamine agonist formulated in a transdermal delivery system. The present study was to investigate the efficacy and safety of the rotigotine transdermal patch in the treatment of early Parkinson's disease. Patients (n = 561) were randomized to rotigotine, Ropinirole, or placebo. The titration period was up to 13 weeks, and there was a minimum dose-maintenance period of 24 weeks for Ropinirole and 33 weeks for rotigotine. The primary endpoint was the proportion of patients with a minimum of 20% decrease in the combined Unified Parkinson's Disease Rating Scale Part II and Part III scores. The responder rate in the rotigotine group was significantly higher than in the placebo group (52% vs. 30%, P < 0.0001). Transdermal rotigotine at doses <= 8 mg/24 h did not show noninferiority to Ropinirole at doses <= 24 mg/day. In a post-hoc subgroup analysis, rotigotine <= 8 mg/24 hours had a similar efficacy to Ropinirole at doses <= 12 mg/day. The rotigotine transdermal patch was well tolerated. The most common adverse events were application-site reactions, nausea, and somnolence. Application-site reactions were predominantly mild or moderate in intensity. In conclusion, the rotigotine transdermal patch represents an effective and safe option for the treatment of patients with early Parkinson's disease. (c) 2007 Movement Disorder Society
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ten year follow up of parkinson s disease patients randomized to initial therapy with Ropinirole or levodopa
Movement Disorders, 2007Co-Authors: Robert A Hauser, Amos D Korczyn, W Poewe, Olivier Rascol, Peter Paul De Deyn, Ray L Watts, Jon A Stoessl, Anthony E LangAbstract:In a 5-year, double-blind study, subjects with Parkinson's disease (PD) who were randomized to initial treatment with Ropinirole had a significantly lower incidence of dyskinesia compared with subjects randomized to levodopa, although Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were significantly more improved in the levodopa group. Subjects who completed the original study were eligible to participate in a long-term extension study conducted according to an open, naturalistic design and were evaluated approximately every 6 months until they had been followed for a total of 10 years. Comparing subjects randomized to initial treatment with Ropinirole (n = 42) and levodopa (n = 27), the incidence of dyskinesia was significantly lower in the Ropinirole group (adjusted odds ratio [OR] = 0.3; 95% confidence interval [CI]: 0.1, 1.0; P = 0.046) and the median time to dyskinesia was significantly longer (adjusted hazard ratio = 0.4; 95% CI: 0.2, 0.8; P = 0.007). The incidence of at least moderate wearing off ("off" time >/=26% of the awake day) was also significantly lower in the Ropinirole group (adjusted OR = 0.3; 95% CI: 0.09, 0.03; P = 0.03). There were no significant differences in change in UPDRS activities of daily living or motor scores, or scores for the 39-item PD questionnaire, Clinical Global Impression, or the Epworth Sleepiness Scale. Early treatment decisions for individual patients depend largely on the anticipated risk of side effects and long-term complications. Both Ropinirole and levodopa are viable treatment options in early PD.
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development of dyskinesias in a 5 year trial of Ropinirole and l dopa
Movement Disorders, 2006Co-Authors: Olivier Rascol, Amos D Korczyn, Carl E Clarke, David J Brooks, Peter Paul De Deyn, Anthony E Lang, Mona AbdallaAbstract:A 5-year trial of Ropinirole and levodopa in early Parkinson's disease showed that Ropinirole is associated with reduced incidence of dyskinesias. This post hoc analysis investigated whether the dyskinesia-sparing benefit of Ropinirole is lost when levodopa is added to the regimen and evaluated other risk factors for developing dyskinesias. Patients receiving levodopa had a significantly higher risk of dyskinesias than those taking Ropinirole monotherapy (hazard ratio [HR], 6.67; 95% confidence interval [CI], 3.23-14.29; P < 0.001). When patients randomized to Ropinirole were treated with supplementary levodopa, the development of dyskinesias was not significantly different from that in those receiving levodopa from the start (HR, 0.80; 95% CI, 0.48-1.33; P = 0.39). However, the onset of dyskinesias was delayed by around 3 years compared with levodopa monotherapy. Adjusted analyses taking into account baseline and on-treatment factors that influenced use of supplementary levodopa or the development of dyskinesias produced similar results. In conclusion, the risk of developing dyskinesias during maintained initial Ropinirole monotherapy is very low. Only once levodopa is added does the risk substantially change. Early use of Ropinirole postpones the onset of dyskinesias, but these benefits decline when levodopa therapy is started, with no evidence of a subsequent rapid "catch-up" or a persisting preventive effect.
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a six month multicentre double blind bromocriptine controlled study of the safety and efficacy of Ropinirole in the treatment of patients with parkinson s disease not optimally controlled by l dopa
Journal of Neural Transmission, 2002Co-Authors: Ehrout R Brunt, Amos D Korczyn, David J Brooks, J L Montastruc, Fabrizio StocchiAbstract:Objectives. To compare the safety and efficacy of Ropinirole and bromocriptine as adjunct therapy in patients with Parkinson's disease (PD) not optimally controlled by L-dopa. Methods. A randomised, double-blind trial in which 555 patients were assigned to three treatment groups according to the level of daily dosage of L-dopa, presence of motor fluctuations, and use of dopamine agonist before study entry. Patient response was defined as at least a 20% reduction in daily L-dopa dose plus: for patients with no prior treatment and no motor fluctuations, a 20% reduction in UPDRS motor score; for patients with motor fluctuations, a 20% reduction in time spent "off"; and for patients already taking an agonist, an improvement on the CGI scale. Results. Safety assessments showed no significant differences in the two treatment groups for patients without prior dopamine-agonist therapy. In the group of patients with prior dopamine-agonist therapy, more patients reported adverse events in the Ropinirole group (90% versus 79%, p <0.001). The proportions of responders tended to be higher in Ropinirole groups compared with bromocriptine groups and, in the subgroup with motor fluctuations, this difference was statistically significant (9.1 % versus 0.0 %, respectively; p <0.05). Conclusions. Both drugs were well tolerated. In patients receiving a relatively high dose of L-dopa and requiring the addition of a dopamine agonist to control motor fluctuations or dyskinesias, Ropinirole was significantly more effective than bromocriptine.
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a five year study of the incidence of dyskinesia in patients with early parkinson s disease who were treated with Ropinirole or levodopa
The New England Journal of Medicine, 2000Co-Authors: Olivier Rascol, Amos D Korczyn, Carl E Clarke, David J Brooks, De Deyn Pp, Anthony E LangAbstract:BACKGROUND: There is debate about whether the initial treatment for patients with Parkinson's disease should be levodopa or a dopamine agonist. METHODS: In this prospective, randomized, double-blind study, we compared the safety and efficacy of the dopamine D2-receptor agonist Ropinirole with that of levodopa over a period of five years in 268 patients with early Parkinson's disease. If symptoms were not adequately controlled by the assigned study medication, patients could receive supplementary levodopa, administered in an open-label fashion. The primary outcome measure was the occurrence of dyskinesia. RESULTS: Eighty-five of the 179 patients in the Ropinirole group (47 percent) and 45 of the 89 patients in the levodopa group (51 percent) completed all five years of the study. In the Ropinirole group 29 of the 85 patients (34 percent) received no levodopa supplementation. The analysis of the time to dyskinesia showed a significant difference in favor of Ropinirole (hazard ratio for remaining free of dyskinesia, 2.82; 95 percent confidence interval, 1.78 to 4.44; P<0.001). At five years, the cumulative incidence of dyskinesia (excluding the three patients who had dyskinesia at base line), regardless of levodopa supplementation, was 20 percent (36 of 177 patients) in the Ropinirole group and 45 percent (40 of 88 patients) in the levodopa group. There was no significant difference between the two groups in the mean change in scores for activities of daily living among those who completed the study. Adverse events led to the early withdrawal from the study of 48 of 179 patients in the Ropinirole group (27 percent) and 29 of 89 patients in the levodopa group (33 percent). The mean (+/-SD) daily doses given by the end of the study were 16.5+/-6.6 mg of Ropinirole (plus 427+/-221 mg of levodopa in patients who received supplementation) and 753+/-398 mg of levodopa (including supplements). CONCLUSIONS: Early Parkinson's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with Ropinirole alone and supplementing it with levodopa if necessary.
Anthony E Lang - One of the best experts on this subject based on the ideXlab platform.
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ten year follow up of parkinson s disease patients randomized to initial therapy with Ropinirole or levodopa
Movement Disorders, 2007Co-Authors: Robert A Hauser, Amos D Korczyn, W Poewe, Olivier Rascol, Peter Paul De Deyn, Ray L Watts, Jon A Stoessl, Anthony E LangAbstract:In a 5-year, double-blind study, subjects with Parkinson's disease (PD) who were randomized to initial treatment with Ropinirole had a significantly lower incidence of dyskinesia compared with subjects randomized to levodopa, although Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were significantly more improved in the levodopa group. Subjects who completed the original study were eligible to participate in a long-term extension study conducted according to an open, naturalistic design and were evaluated approximately every 6 months until they had been followed for a total of 10 years. Comparing subjects randomized to initial treatment with Ropinirole (n = 42) and levodopa (n = 27), the incidence of dyskinesia was significantly lower in the Ropinirole group (adjusted odds ratio [OR] = 0.3; 95% confidence interval [CI]: 0.1, 1.0; P = 0.046) and the median time to dyskinesia was significantly longer (adjusted hazard ratio = 0.4; 95% CI: 0.2, 0.8; P = 0.007). The incidence of at least moderate wearing off ("off" time >/=26% of the awake day) was also significantly lower in the Ropinirole group (adjusted OR = 0.3; 95% CI: 0.09, 0.03; P = 0.03). There were no significant differences in change in UPDRS activities of daily living or motor scores, or scores for the 39-item PD questionnaire, Clinical Global Impression, or the Epworth Sleepiness Scale. Early treatment decisions for individual patients depend largely on the anticipated risk of side effects and long-term complications. Both Ropinirole and levodopa are viable treatment options in early PD.
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development of dyskinesias in a 5 year trial of Ropinirole and l dopa
Movement Disorders, 2006Co-Authors: Olivier Rascol, Amos D Korczyn, Carl E Clarke, David J Brooks, Peter Paul De Deyn, Anthony E Lang, Mona AbdallaAbstract:A 5-year trial of Ropinirole and levodopa in early Parkinson's disease showed that Ropinirole is associated with reduced incidence of dyskinesias. This post hoc analysis investigated whether the dyskinesia-sparing benefit of Ropinirole is lost when levodopa is added to the regimen and evaluated other risk factors for developing dyskinesias. Patients receiving levodopa had a significantly higher risk of dyskinesias than those taking Ropinirole monotherapy (hazard ratio [HR], 6.67; 95% confidence interval [CI], 3.23-14.29; P < 0.001). When patients randomized to Ropinirole were treated with supplementary levodopa, the development of dyskinesias was not significantly different from that in those receiving levodopa from the start (HR, 0.80; 95% CI, 0.48-1.33; P = 0.39). However, the onset of dyskinesias was delayed by around 3 years compared with levodopa monotherapy. Adjusted analyses taking into account baseline and on-treatment factors that influenced use of supplementary levodopa or the development of dyskinesias produced similar results. In conclusion, the risk of developing dyskinesias during maintained initial Ropinirole monotherapy is very low. Only once levodopa is added does the risk substantially change. Early use of Ropinirole postpones the onset of dyskinesias, but these benefits decline when levodopa therapy is started, with no evidence of a subsequent rapid "catch-up" or a persisting preventive effect.
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slower progression of parkinson s disease with Ropinirole versus levodopa the real pet study
Annals of Neurology, 2003Co-Authors: Alan L Whone, Olivier Rascol, Anthony E Lang, Ray L Watts, Jon A Stoessl, Margaret R Davis, Sven N Reske, Claude Nahmias, Maria J Ribeiro, Philippe RemyAbstract:Preclinical studies suggest Ropinirole (a D2/D3 dopamine agonist) may be neuroprotective in Parkinson's disease (PD), and a pilot clinical study using 18F-dopa positron emission tomography (PET) suggested a slower loss of striatal dopamine storage with Ropinirole compared with levodopa. This prospective, 2-year, randomized, double-blind, multinational study compared the rates of loss of dopamine-terminal function in de novo patients with clinical and 18F-dopa PET evidence of early PD, randomized 1 to 1 to receive either Ropinirole or levodopa. The primary outcome measure was reduction in putamen 18F-dopa uptake (Ki) between baseline and 2-year PET. Of 186, 162 randomized patients were eligible for analysis. A blinded, central, region-of-interest analysis showed a significantly lower reduction (p = 0.022) in putamen Ki over 2 years with Ropinirole (−13.4%; n = 68) compared with levodopa (−20.3%; n = 59; 95% confidence interval [CI], 0.65–13.06). Statistical parametric mapping localized lesser reductions in 18F-dopa uptake in the putamen and substantia nigra with Ropinirole. The greatest Ki decrease in each group was in the putamen (Ropinirole, −14.1%; levodopa, −22.9%; 95% CI, 4.24–13.3), but the decrease was significantly lower with Ropinirole compared with levodopa (p < 0.001). Ropinirole is associated with slower progression of PD than levodopa as assessed by 18F-dopa PET. Ann Neurol 2003
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slower progression of parkinson s disease with Ropinirole versus levodopa the real pet study
Annals of Neurology, 2003Co-Authors: Alan L Whone, Olivier Rascol, Anthony E Lang, Ray L Watts, Jon A Stoessl, Margaret R Davis, Sven N Reske, Claude Nahmias, Maria J Ribeiro, Philippe RemyAbstract:Preclinical studies suggest Ropinirole (a D2/D3 dopamine agonist) may be neuroprotective in Parkinson's disease (PD), and a pilot clinical study using (18)F-dopa positron emission tomography (PET) suggested a slower loss of striatal dopamine storage with Ropinirole compared with levodopa. This prospective, 2-year, randomized, double-blind, multinational study compared the rates of loss of dopamine-terminal function in de novo patients with clinical and (18)F-dopa PET evidence of early PD, randomized 1 to 1 to receive either Ropinirole or levodopa. The primary outcome measure was reduction in putamen (18)F-dopa uptake (Ki) between baseline and 2-year PET. Of 186, 162 randomized patients were eligible for analysis. A blinded, central, region-of-interest analysis showed a significantly lower reduction (p = 0.022) in putamen Ki over 2 years with Ropinirole (-13.4%; n = 68) compared with levodopa (-20.3%; n = 59; 95% confidence interval [CI], 0.65-13.06). Statistical parametric mapping localized lesser reductions in (18)F-dopa uptake in the putamen and substantia nigra with Ropinirole. The greatest Ki decrease in each group was in the putamen (Ropinirole, -14.1%; levodopa, -22.9%; 95% CI, 4.24-13.3), but the decrease was significantly lower with Ropinirole compared with levodopa (p < 0.001). Ropinirole is associated with slower progression of PD than levodopa as assessed by (18)F-dopa PET.
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a five year study of the incidence of dyskinesia in patients with early parkinson s disease who were treated with Ropinirole or levodopa
The New England Journal of Medicine, 2000Co-Authors: Olivier Rascol, Amos D Korczyn, Carl E Clarke, David J Brooks, De Deyn Pp, Anthony E LangAbstract:BACKGROUND: There is debate about whether the initial treatment for patients with Parkinson's disease should be levodopa or a dopamine agonist. METHODS: In this prospective, randomized, double-blind study, we compared the safety and efficacy of the dopamine D2-receptor agonist Ropinirole with that of levodopa over a period of five years in 268 patients with early Parkinson's disease. If symptoms were not adequately controlled by the assigned study medication, patients could receive supplementary levodopa, administered in an open-label fashion. The primary outcome measure was the occurrence of dyskinesia. RESULTS: Eighty-five of the 179 patients in the Ropinirole group (47 percent) and 45 of the 89 patients in the levodopa group (51 percent) completed all five years of the study. In the Ropinirole group 29 of the 85 patients (34 percent) received no levodopa supplementation. The analysis of the time to dyskinesia showed a significant difference in favor of Ropinirole (hazard ratio for remaining free of dyskinesia, 2.82; 95 percent confidence interval, 1.78 to 4.44; P<0.001). At five years, the cumulative incidence of dyskinesia (excluding the three patients who had dyskinesia at base line), regardless of levodopa supplementation, was 20 percent (36 of 177 patients) in the Ropinirole group and 45 percent (40 of 88 patients) in the levodopa group. There was no significant difference between the two groups in the mean change in scores for activities of daily living among those who completed the study. Adverse events led to the early withdrawal from the study of 48 of 179 patients in the Ropinirole group (27 percent) and 29 of 89 patients in the levodopa group (33 percent). The mean (+/-SD) daily doses given by the end of the study were 16.5+/-6.6 mg of Ropinirole (plus 427+/-221 mg of levodopa in patients who received supplementation) and 753+/-398 mg of levodopa (including supplements). CONCLUSIONS: Early Parkinson's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with Ropinirole alone and supplementing it with levodopa if necessary.
Olivier Rascol - One of the best experts on this subject based on the ideXlab platform.
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ten year follow up of parkinson s disease patients randomized to initial therapy with Ropinirole or levodopa
Movement Disorders, 2007Co-Authors: Robert A Hauser, Amos D Korczyn, W Poewe, Olivier Rascol, Peter Paul De Deyn, Ray L Watts, Jon A Stoessl, Anthony E LangAbstract:In a 5-year, double-blind study, subjects with Parkinson's disease (PD) who were randomized to initial treatment with Ropinirole had a significantly lower incidence of dyskinesia compared with subjects randomized to levodopa, although Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were significantly more improved in the levodopa group. Subjects who completed the original study were eligible to participate in a long-term extension study conducted according to an open, naturalistic design and were evaluated approximately every 6 months until they had been followed for a total of 10 years. Comparing subjects randomized to initial treatment with Ropinirole (n = 42) and levodopa (n = 27), the incidence of dyskinesia was significantly lower in the Ropinirole group (adjusted odds ratio [OR] = 0.3; 95% confidence interval [CI]: 0.1, 1.0; P = 0.046) and the median time to dyskinesia was significantly longer (adjusted hazard ratio = 0.4; 95% CI: 0.2, 0.8; P = 0.007). The incidence of at least moderate wearing off ("off" time >/=26% of the awake day) was also significantly lower in the Ropinirole group (adjusted OR = 0.3; 95% CI: 0.09, 0.03; P = 0.03). There were no significant differences in change in UPDRS activities of daily living or motor scores, or scores for the 39-item PD questionnaire, Clinical Global Impression, or the Epworth Sleepiness Scale. Early treatment decisions for individual patients depend largely on the anticipated risk of side effects and long-term complications. Both Ropinirole and levodopa are viable treatment options in early PD.
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development of dyskinesias in a 5 year trial of Ropinirole and l dopa
Movement Disorders, 2006Co-Authors: Olivier Rascol, Amos D Korczyn, Carl E Clarke, David J Brooks, Peter Paul De Deyn, Anthony E Lang, Mona AbdallaAbstract:A 5-year trial of Ropinirole and levodopa in early Parkinson's disease showed that Ropinirole is associated with reduced incidence of dyskinesias. This post hoc analysis investigated whether the dyskinesia-sparing benefit of Ropinirole is lost when levodopa is added to the regimen and evaluated other risk factors for developing dyskinesias. Patients receiving levodopa had a significantly higher risk of dyskinesias than those taking Ropinirole monotherapy (hazard ratio [HR], 6.67; 95% confidence interval [CI], 3.23-14.29; P < 0.001). When patients randomized to Ropinirole were treated with supplementary levodopa, the development of dyskinesias was not significantly different from that in those receiving levodopa from the start (HR, 0.80; 95% CI, 0.48-1.33; P = 0.39). However, the onset of dyskinesias was delayed by around 3 years compared with levodopa monotherapy. Adjusted analyses taking into account baseline and on-treatment factors that influenced use of supplementary levodopa or the development of dyskinesias produced similar results. In conclusion, the risk of developing dyskinesias during maintained initial Ropinirole monotherapy is very low. Only once levodopa is added does the risk substantially change. Early use of Ropinirole postpones the onset of dyskinesias, but these benefits decline when levodopa therapy is started, with no evidence of a subsequent rapid "catch-up" or a persisting preventive effect.
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slower progression of parkinson s disease with Ropinirole versus levodopa the real pet study
Annals of Neurology, 2003Co-Authors: Alan L Whone, Olivier Rascol, Anthony E Lang, Ray L Watts, Jon A Stoessl, Margaret R Davis, Sven N Reske, Claude Nahmias, Maria J Ribeiro, Philippe RemyAbstract:Preclinical studies suggest Ropinirole (a D2/D3 dopamine agonist) may be neuroprotective in Parkinson's disease (PD), and a pilot clinical study using 18F-dopa positron emission tomography (PET) suggested a slower loss of striatal dopamine storage with Ropinirole compared with levodopa. This prospective, 2-year, randomized, double-blind, multinational study compared the rates of loss of dopamine-terminal function in de novo patients with clinical and 18F-dopa PET evidence of early PD, randomized 1 to 1 to receive either Ropinirole or levodopa. The primary outcome measure was reduction in putamen 18F-dopa uptake (Ki) between baseline and 2-year PET. Of 186, 162 randomized patients were eligible for analysis. A blinded, central, region-of-interest analysis showed a significantly lower reduction (p = 0.022) in putamen Ki over 2 years with Ropinirole (−13.4%; n = 68) compared with levodopa (−20.3%; n = 59; 95% confidence interval [CI], 0.65–13.06). Statistical parametric mapping localized lesser reductions in 18F-dopa uptake in the putamen and substantia nigra with Ropinirole. The greatest Ki decrease in each group was in the putamen (Ropinirole, −14.1%; levodopa, −22.9%; 95% CI, 4.24–13.3), but the decrease was significantly lower with Ropinirole compared with levodopa (p < 0.001). Ropinirole is associated with slower progression of PD than levodopa as assessed by 18F-dopa PET. Ann Neurol 2003
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slower progression of parkinson s disease with Ropinirole versus levodopa the real pet study
Annals of Neurology, 2003Co-Authors: Alan L Whone, Olivier Rascol, Anthony E Lang, Ray L Watts, Jon A Stoessl, Margaret R Davis, Sven N Reske, Claude Nahmias, Maria J Ribeiro, Philippe RemyAbstract:Preclinical studies suggest Ropinirole (a D2/D3 dopamine agonist) may be neuroprotective in Parkinson's disease (PD), and a pilot clinical study using (18)F-dopa positron emission tomography (PET) suggested a slower loss of striatal dopamine storage with Ropinirole compared with levodopa. This prospective, 2-year, randomized, double-blind, multinational study compared the rates of loss of dopamine-terminal function in de novo patients with clinical and (18)F-dopa PET evidence of early PD, randomized 1 to 1 to receive either Ropinirole or levodopa. The primary outcome measure was reduction in putamen (18)F-dopa uptake (Ki) between baseline and 2-year PET. Of 186, 162 randomized patients were eligible for analysis. A blinded, central, region-of-interest analysis showed a significantly lower reduction (p = 0.022) in putamen Ki over 2 years with Ropinirole (-13.4%; n = 68) compared with levodopa (-20.3%; n = 59; 95% confidence interval [CI], 0.65-13.06). Statistical parametric mapping localized lesser reductions in (18)F-dopa uptake in the putamen and substantia nigra with Ropinirole. The greatest Ki decrease in each group was in the putamen (Ropinirole, -14.1%; levodopa, -22.9%; 95% CI, 4.24-13.3), but the decrease was significantly lower with Ropinirole compared with levodopa (p < 0.001). Ropinirole is associated with slower progression of PD than levodopa as assessed by (18)F-dopa PET.
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a five year study of the incidence of dyskinesia in patients with early parkinson s disease who were treated with Ropinirole or levodopa
The New England Journal of Medicine, 2000Co-Authors: Olivier Rascol, Amos D Korczyn, Carl E Clarke, David J Brooks, De Deyn Pp, Anthony E LangAbstract:BACKGROUND: There is debate about whether the initial treatment for patients with Parkinson's disease should be levodopa or a dopamine agonist. METHODS: In this prospective, randomized, double-blind study, we compared the safety and efficacy of the dopamine D2-receptor agonist Ropinirole with that of levodopa over a period of five years in 268 patients with early Parkinson's disease. If symptoms were not adequately controlled by the assigned study medication, patients could receive supplementary levodopa, administered in an open-label fashion. The primary outcome measure was the occurrence of dyskinesia. RESULTS: Eighty-five of the 179 patients in the Ropinirole group (47 percent) and 45 of the 89 patients in the levodopa group (51 percent) completed all five years of the study. In the Ropinirole group 29 of the 85 patients (34 percent) received no levodopa supplementation. The analysis of the time to dyskinesia showed a significant difference in favor of Ropinirole (hazard ratio for remaining free of dyskinesia, 2.82; 95 percent confidence interval, 1.78 to 4.44; P<0.001). At five years, the cumulative incidence of dyskinesia (excluding the three patients who had dyskinesia at base line), regardless of levodopa supplementation, was 20 percent (36 of 177 patients) in the Ropinirole group and 45 percent (40 of 88 patients) in the levodopa group. There was no significant difference between the two groups in the mean change in scores for activities of daily living among those who completed the study. Adverse events led to the early withdrawal from the study of 48 of 179 patients in the Ropinirole group (27 percent) and 29 of 89 patients in the levodopa group (33 percent). The mean (+/-SD) daily doses given by the end of the study were 16.5+/-6.6 mg of Ropinirole (plus 427+/-221 mg of levodopa in patients who received supplementation) and 753+/-398 mg of levodopa (including supplements). CONCLUSIONS: Early Parkinson's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with Ropinirole alone and supplementing it with levodopa if necessary.
Mark J Millan - One of the best experts on this subject based on the ideXlab platform.
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dopamine d2 d3 receptor heteromers pharmacological properties and therapeutic significance
Current Opinion in Pharmacology, 2010Co-Authors: Roberto Maggio, Mark J MillanAbstract:Heteromerization of dopamine receptors has been shown for both the D 1 /D 5 and D 2 /D 3 /D 4 receptor families, which couple positively and negatively, respectively, to adenylyl cyclase. The present article reviews data on dopamine heteromers formed by D 3 , focusing in particular on associations with their D 2 counterparts. Certain antiparkinsonian agents, like the preferential and high efficacy D 3 > D 2 agonists, pramipexole, and Ropinirole, show amplified potency at D 2 –D 3 heteromers versus constituent monomers. Accordingly, in cells cotransfected with D 2 and D 3 receptors, pramipexole, and Ropinirole suppress forskolin (FK)-stimulated cAMP production with higher potencies as compared to cells transfected with D 2 or D 3 receptors only. Furthermore, in cells cotransfected with D 2 and an excess of D 3 receptors, the partial agonists aripiprazole, S33592, bifeprunox, N -desmethylclozapine, and preclamol lose agonist properties and abolish the actions of quinpirole. Then, partial agonists are transformed into antagonists upon cotransfection of D 2 with an excess of D 3 receptors. A hypothetical relationship of the above observations to the pathophysiology and possibly treatment of neuropsychiatric diseases is discussed.
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neuroprotective effects of the novel d3 d2 receptor agonist and antiparkinson agent s32504 in vitro against 1 methyl 4 phenylpyridinium mpp and in vivo against 1 methyl 4 phenyl 1 2 3 6 tetrahydropyridine mptp a comparison to Ropinirole
Experimental Neurology, 2003Co-Authors: Jeffrey N Joyce, Steve Presgraves, Lynn Renish, Sabinne Borwege, Tracy Osredkar, Diane Hagner, Maria Replogle, Mateo Pazsoldan, Mark J MillanAbstract:Abstract The novel naphtoxazine derivative and preferential D3 vs D2 receptor agonist, S32504, restores perturbed motor function in rodent and primate models of antiparkinsonian activity with a potency superior to those of two further, preferential D3 receptor agonists, pramipexole and Ropinirole. However, potential neuroprotective properties of S32054 have not, to date, been evaluated. Herein, employing several measures of cellular integrity, we demonstrate that S32504 robustly, concentration-dependently and completely protects terminally differentiated SH-SY5Y cells against 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in vitro. Further, S32504 was substantially more potent than pramipexole and Ropinirole, the latter of which was neurotoxic at high concentrations. In vivo, subchronic treatment with low (0.25 mg/kg) and high (2.5 mg/kg) doses of S32504 prior to and during treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP, provided complete protection against MPTP-induced tyrosine hydroxylase immunoreactive (TH-IR) neuronal death in the substantia nigra pars compacta and ventral tegmental area. A high dose of Ropinirole (2.5 mg/kg) provided some protection but statistical significance was not attained, and a low dose (0.25 mg/kg) was ineffective. Neither drug afforded protection against the MPTP-induced loss of DA fibers in the striatum, as measured by TH-IR and dopamine transporter immunoreactive fiber counts. In conclusion, the novel naphotoxazine and dopaminergic agonist, S32504, robustly protects dopaminergic neurones against the neurotoxic effects of MPP+ and MPTP in in vitro and in vivo models, respectively. The underlying mechanisms and therapeutic pertinence of these actions will be of interest to further evaluate in view of its potent actions in behavioral models of antiparkinson activity.
