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E. K. Tan - One of the best experts on this subject based on the ideXlab platform.
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Piribedil induced sleep attacks in parkinson s disease
Fundamental & Clinical Pharmacology, 2003Co-Authors: E. K. TanAbstract:‘Sleep attacks’, episodes of sudden onset of sleep without any prodromal symptoms, were initially described in patients with Parkinson's disease (PD) taking the newer dopamine agonists pramipexole and ropinirole. Piribedil, a nonergot agonist with both D2 and D3 agonist action, is an effective antiparkinsonian medication. However, there are very few reports of Piribedil-induced sleep attacks in PD. Among 50 PD patients seen at our Movement Disorder Clinic who had recently taken Piribedil, we identified three (6%) who satisfied the clinical description of sleep attacks. Here we provide details of the clinical characteristics of Piribedil-induced sleep attacks in these PD patients.
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Piribedil‐induced sleep attacks in Parkinson's disease
Fundamental & clinical pharmacology, 2003Co-Authors: E. K. TanAbstract:‘Sleep attacks’, episodes of sudden onset of sleep without any prodromal symptoms, were initially described in patients with Parkinson's disease (PD) taking the newer dopamine agonists pramipexole and ropinirole. Piribedil, a nonergot agonist with both D2 and D3 agonist action, is an effective antiparkinsonian medication. However, there are very few reports of Piribedil-induced sleep attacks in PD. Among 50 PD patients seen at our Movement Disorder Clinic who had recently taken Piribedil, we identified three (6%) who satisfied the clinical description of sleep attacks. Here we provide details of the clinical characteristics of Piribedil-induced sleep attacks in these PD patients.
Peter Jenner - One of the best experts on this subject based on the ideXlab platform.
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switching from levodopa to the long acting dopamine d2 d3 agonist Piribedil reduces the expression of dyskinesia while maintaining effective motor activity in mptp treated primates
Clinical Neuropharmacology, 2006Co-Authors: Lance A. Smith, Susanna Del Signore, Michael J. Jackson, Sarah Rose, Louisa Johnston, Mikko Kuoppamaki, Ghassan Albarghouthy, Peter JennerAbstract:Background: The control of motor complications following dopaminergic medication in late-stage Parkinson disease remains problematic. Objective: We now investigate the potential of oral administration of the long-acting dopamine D 2 /D 3 agonist Piribedil to decrease the expression of dyskinesia induced by prior exposure to levodopa in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-treated primates. Methods: MPTP-treated common marmosets were treated with equieffective doses of levodopa (10.0-12.5 mg/kg PO, twice daily) or Piribedil (3.0-4.0 mg/kg PO, once daily) for 30 days and then switched to the alternative treatment for a further 35 days. Results: Levodopa administration markedly improved motor function, but dyskinesia rapidly appeared and intensified as treatment progressed. Administration of Piribedil produced a similar reversal of MPTP-induced motor deficits but with comparatively mild dyskinesia. On switching from levodopa to Piribedil, the intensity of dyskinesia decreased without altering the improvement in motor deficits. However, on switching from Piribedil to levodopa, the rapid increase in dyskinesia despite the improvement in motor function being maintained suggests that Piribedil also primes for but does not markedly express dyskinesia. Conclusion: The study confirms the low dyskinesia expression resulting from Piribedil treatment compared with an equieffective dose of levodopa. Importantly, the results show that switching from levodopa to Piribedil rapidly results in a sustained decrease in dyskinesia intensity.
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Repeated administration of Piribedil induces less dyskinesia than L-dopa in MPTP-treated common marmosets: A behavioural and biochemical investigation
Movement disorders : official journal of the Movement Disorder Society, 2002Co-Authors: Lance A. Smith, Susanna Del Signore, Céline Bonhomme, Claire Chezaubernard, Banu C. Tel, Michael J. Jackson, Matthew J. Hansard, Rogelio Braceras, Sarah Rose, Peter JennerAbstract:Piribedil ([1-(3,4-methylenedioxybenzyl)-4-(2-pyrimidinyl)piperazine]; S 4200) is a dopamine agonist with equal affinity for D2/D3 dopamine receptors effective in treating Parkinson's disease as monotherapy or as an adjunct to levodopa (L-dopa). However, its ability to prime basal ganglia for the appearance of dyskinesia is unknown. We now report on the ability of repeated administration of Piribedil to induce dyskinesia in drug naive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -lesioned common marmosets compared with L-dopa and its actions on the direct and indirect striatal outflow pathways. Administration of Piribedil (4.0–5.0 mg/kg orally) or L-dopa (12.5 mg/kg orally plus carbidopa 12.5 mg/kg orally twice daily) produced equivalent increases in locomotor activity and reversal of motor deficits over a 28-day study period. Administration of L-dopa resulted in the progressive development of marked dyskinesia over the period of study. In contrast, administration of Piribedil produced a significantly lower degree and intensity of dyskinesia. Surprisingly, Piribedil caused an increase in vigilance and alertness compared to L-dopa, which may relate to the recently discovered α2-noradrenergic antagonist properties of Piribedil. The behavioural differences between Piribedil and L-dopa are reflected in the biochemical changes associated with the direct striatal output pathway. Administration of L-dopa or Piribedil did not reverse the MPTP-induced up-regulation of preproenkephalin A mRNA in rostral or caudal areas of the putamen or caudate nucleus. In contrast, administration of either Piribedil or L-dopa reversed the downregulation of preprotachykinin mRNA induced by MPTP in rostral and caudal striatum. L-dopa, but not Piribedil, reversed the decrease in preproenkephalin B mRNA produced by MPTP treatment. © 2002 Movement Disorder Society
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Transdermal administration of Piribedil reverses MPTP-induced motor deficits in the common marmoset
Clinical neuropharmacology, 2000Co-Authors: Lance A. Smith, Michael G Jackson, Céline Bonhomme, Claire Chezaubernard, Ronald K. B. Pearce, Peter JennerAbstract:The ability of transdermal administration of the dopamine D2/D3 agonist Piribedil (1-[3,4-methylenedioxybenzyl)]-4-[(2-pyrimidinyl)]piperazine) to reverse hypokinesia and other motor deficits observed in MPTP-treated common marmosets was investigated. Piribedil (2.5-10.0 mg/animal), applied directly to the skin of the abdomen as a paste, produced a long-lasting and concentration-dependent reversal of motor deficits. The antiparkinsonian actions of Piribedil occurred within 10 minutes of drug administration and lasted as long as 10 hours. Transdermally applied Piribedil produced a pattern of locomotor activity characteristic of normal motor behavior in this species. Symptoms of nausea (marked excessive salivation, retching, and/or vomiting) were not observed after transdermal application of Piribedil. Additionally, pretreatment with the peripheral dopamine antagonist domperidone enhanced the antiparkinsonian effects of Piribedil. Application to the skin of monolayer or bilayer patches impregnated with Piribedil also produced a marked increase in locomotor activity and reversal of motor deficits. After application of various patch fractions (whole, one-half, or one-fourth), the increase in locomotor activity and reversal of disability correlated well with the surface area of skin covered. Measurement of serum levels of Piribedil after single application of bilayer patches showed a positive relationship between drug levels and antiparkinsonian activity. Repeated daily application of Piribedil bilayer patches for 5 days to MPTP-treated common marmosets primed to show dyskinesia by previous exposure to L-Dopa produced antiparkinsonian activity accompanied by dyskinetic movements. Transdermal administration of dopamine agonists such as Piribedil may provide a useful means of producing a long-lasting reversal of motor deficits in Parkinson's disease while avoiding acute adverse effects such as nausea.
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An appraisal of the antiparkinsonian activity of Piribedil in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets.
Movement disorders : official journal of the Movement Disorder Society, 1996Co-Authors: Lance A. Smith, Peter Jenner, Maria De Salvia, C. David MarsdenAbstract:The D2 dopamine agonist Piribedil is not widely used in the treatment of Parkinson's disease because it was thought to be effective mainly on parkinsonian tremor and to produce a high incidence of peripheral side effects, particular nausea. In this study, we used 1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine (MPTP)–treated primates to reevaluate the antiparkinsonian ability of Piribedil after its oral administration in the presence or absence of domperidone pretreatment. Adult common marmosets (Callithrix jacchus) were treated with the nigral toxin MPTP to induce a parkinsonian syndrome characterised primarily by brady kinesia and other motor deficits. Oral administration of a solution of Piribedil [1–(3,4–methylenedioxybenzyl)–4–(2–pyrimidinyl) piperazine] produced a dose–related reversal of all MPTP locomotor and behavioural deficits. However, this effect was short lived and associated with unwanted effects, particular nausea and retching, which clearly hindered locomotion. In contrast, after pretreatment with the peripheral dopamine antagonist domperidone, administration of Piribedil did not induce nausea or retching in MPTP-treated marmosets. In these animals, Piribedil caused a more marked and and longer lasting enhancement of locomotor activity and a further reduction in behavioural deficits than that observed after administration of Piribedil alone. In addition, Piribedil induced increased vigilance and awareness. These data show that Piribedil can reverse akinesia and rigidity in MPTP-treated primates. In addition, they show the drug to be effective without peripheral side effects when used in conjuction with domperidone. These data indicate that Piribedil should be an effective monotherapy for Parkinson's disease.
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maladie de parkinson mecanismes physiopathologiques et effets du Piribedil
Journal of Neurology, 1993Co-Authors: Peter JennerAbstract:Lors de la maladie de Parkinson, la degenerescence des cellules dopaminergiques situees dans la zona compacta du locus niger reste de cause inconnue. La capacite de la 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine (MPTP), toxine selective du locus niger, a detruire selectivement les cellules dopaminergiques de ce noyau (via son metabolite MPP+) en inhibant le complexe I du cycle energetique mitochondrial, pourrait representer un debut d'explication. En effet, des etudes recentes effectuees post-mortem sur le tissu cerebral ont suggere l'existence, au cours de la maladie de Parkinson, d'un processus toxique evolutif affectant le locus niger et entrainant un exces de peroxydation lipidique. Ce processus semble egalement impliquer une interruption du fonctionnement mitochondrial, avec une hyperactivite de la superoxyde dismutase mitochondriale ainsi que des anomalies du complexe I. Ces modifications pourraient a leur tour etre liees a une augmentation selective de la teneur totale en fer du locus niger, couplee a une diminution generalisee de la teneur cerebrale en ferritine. Le Piribedil est utilise dans le traitement symptomatique de la maladie de Parkinson; il est particulierement efficace sur le tremblement. Le Piribedil se comporte (ainsi que ses metabolites) comme un agoniste des recepteurs dopaminergiques D2. Toutefois nos travaux montrent que, contrairement aux autres agonistes dopaminergiques, le Piribedil interagit in vivo avec les recepteurs dopaminergiques du locus niger et du nucleus accumbens, mais non avec ceux du striatum. Lors de la maladie de Parkinson, les effets benefiques du Piribedil peuvent etre limites par la survenue de nausees et de somnolence. En effet, chez le primate traite par le MPTP, le Piribedil corrige les deficits moteurs mais peut entrainer des effets secondaires genants. Toutefois, un traitement prealable par la domperidone, antagoniste peripherique des recepteurs dopaminergiques, previent ces effets indesirables et le Piribedil induit une correction profonde et prolongee de toutes les composantes du syndrome moteur. Ces resultats suggerent qu'en association avec la domperidone, le Piribedil pourrait representer une monotherapie efficace de la maladie de Parkinson.
Tong Zhang - One of the best experts on this subject based on the ideXlab platform.
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protective effects of dopamine d2 d3 receptor agonist Piribedil on learning and memory of rats exposed to global cerebral ischemia reperfusion
Neuroscience Letters, 2018Co-Authors: Wenzhu Wang, Lixu Liu, Chen Chen, Peng Jiang, Tong ZhangAbstract:Abstract Global cerebral ischemia-reperfusion (GCI/R) may occur after any of several clinical conditions such as cardiac arrest and anesthetic accident. Some dopamine receptor agonists possess neuroprotective effects. However, some of them may produce side effects during treatment. Piribedil, which is a dopamine D2/D3 receptor agonist, has fewer side effects and is well tolerated. This study investigated the effects of Piribedil on learning and memory of rats with GCI/R according to modified neurological severity score (mNSS) scoring and Morris water maze test (MWM). Rats with GCI/R were treated with Piribedil 25 or 50 mg/kg/d, and mNSS was performed at 6 h, 1 day, 3 days, and 1 and 2 weeks after injury. The MWM test was employed to evaluate learning and memory of rats at 1 and 2 weeks after injury. The results showed treatment with Piribedil reduced the mNSS score and prolonged the time in the target quadrant compared with untreated rats although no obvious differences of the 25 and 50 mg/kg/d Piribedil intervention groups were observed statistically. Piribedil is effective in improving the neurological function and learning and memory of rats after GCI/R.
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Protective effects of dopamine D2/D3 receptor agonist Piribedil on learning and memory of rats exposed to global cerebral ischemia-reperfusion.
Neuroscience letters, 2018Co-Authors: Wenzhu Wang, Lixu Liu, Chen Chen, Peng Jiang, Tong ZhangAbstract:Abstract Global cerebral ischemia-reperfusion (GCI/R) may occur after any of several clinical conditions such as cardiac arrest and anesthetic accident. Some dopamine receptor agonists possess neuroprotective effects. However, some of them may produce side effects during treatment. Piribedil, which is a dopamine D2/D3 receptor agonist, has fewer side effects and is well tolerated. This study investigated the effects of Piribedil on learning and memory of rats with GCI/R according to modified neurological severity score (mNSS) scoring and Morris water maze test (MWM). Rats with GCI/R were treated with Piribedil 25 or 50 mg/kg/d, and mNSS was performed at 6 h, 1 day, 3 days, and 1 and 2 weeks after injury. The MWM test was employed to evaluate learning and memory of rats at 1 and 2 weeks after injury. The results showed treatment with Piribedil reduced the mNSS score and prolonged the time in the target quadrant compared with untreated rats although no obvious differences of the 25 and 50 mg/kg/d Piribedil intervention groups were observed statistically. Piribedil is effective in improving the neurological function and learning and memory of rats after GCI/R.
Lance A. Smith - One of the best experts on this subject based on the ideXlab platform.
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switching from levodopa to the long acting dopamine d2 d3 agonist Piribedil reduces the expression of dyskinesia while maintaining effective motor activity in mptp treated primates
Clinical Neuropharmacology, 2006Co-Authors: Lance A. Smith, Susanna Del Signore, Michael J. Jackson, Sarah Rose, Louisa Johnston, Mikko Kuoppamaki, Ghassan Albarghouthy, Peter JennerAbstract:Background: The control of motor complications following dopaminergic medication in late-stage Parkinson disease remains problematic. Objective: We now investigate the potential of oral administration of the long-acting dopamine D 2 /D 3 agonist Piribedil to decrease the expression of dyskinesia induced by prior exposure to levodopa in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-treated primates. Methods: MPTP-treated common marmosets were treated with equieffective doses of levodopa (10.0-12.5 mg/kg PO, twice daily) or Piribedil (3.0-4.0 mg/kg PO, once daily) for 30 days and then switched to the alternative treatment for a further 35 days. Results: Levodopa administration markedly improved motor function, but dyskinesia rapidly appeared and intensified as treatment progressed. Administration of Piribedil produced a similar reversal of MPTP-induced motor deficits but with comparatively mild dyskinesia. On switching from levodopa to Piribedil, the intensity of dyskinesia decreased without altering the improvement in motor deficits. However, on switching from Piribedil to levodopa, the rapid increase in dyskinesia despite the improvement in motor function being maintained suggests that Piribedil also primes for but does not markedly express dyskinesia. Conclusion: The study confirms the low dyskinesia expression resulting from Piribedil treatment compared with an equieffective dose of levodopa. Importantly, the results show that switching from levodopa to Piribedil rapidly results in a sustained decrease in dyskinesia intensity.
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Repeated administration of Piribedil induces less dyskinesia than L-dopa in MPTP-treated common marmosets: A behavioural and biochemical investigation
Movement disorders : official journal of the Movement Disorder Society, 2002Co-Authors: Lance A. Smith, Susanna Del Signore, Céline Bonhomme, Claire Chezaubernard, Banu C. Tel, Michael J. Jackson, Matthew J. Hansard, Rogelio Braceras, Sarah Rose, Peter JennerAbstract:Piribedil ([1-(3,4-methylenedioxybenzyl)-4-(2-pyrimidinyl)piperazine]; S 4200) is a dopamine agonist with equal affinity for D2/D3 dopamine receptors effective in treating Parkinson's disease as monotherapy or as an adjunct to levodopa (L-dopa). However, its ability to prime basal ganglia for the appearance of dyskinesia is unknown. We now report on the ability of repeated administration of Piribedil to induce dyskinesia in drug naive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -lesioned common marmosets compared with L-dopa and its actions on the direct and indirect striatal outflow pathways. Administration of Piribedil (4.0–5.0 mg/kg orally) or L-dopa (12.5 mg/kg orally plus carbidopa 12.5 mg/kg orally twice daily) produced equivalent increases in locomotor activity and reversal of motor deficits over a 28-day study period. Administration of L-dopa resulted in the progressive development of marked dyskinesia over the period of study. In contrast, administration of Piribedil produced a significantly lower degree and intensity of dyskinesia. Surprisingly, Piribedil caused an increase in vigilance and alertness compared to L-dopa, which may relate to the recently discovered α2-noradrenergic antagonist properties of Piribedil. The behavioural differences between Piribedil and L-dopa are reflected in the biochemical changes associated with the direct striatal output pathway. Administration of L-dopa or Piribedil did not reverse the MPTP-induced up-regulation of preproenkephalin A mRNA in rostral or caudal areas of the putamen or caudate nucleus. In contrast, administration of either Piribedil or L-dopa reversed the downregulation of preprotachykinin mRNA induced by MPTP in rostral and caudal striatum. L-dopa, but not Piribedil, reversed the decrease in preproenkephalin B mRNA produced by MPTP treatment. © 2002 Movement Disorder Society
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Transdermal administration of Piribedil reverses MPTP-induced motor deficits in the common marmoset
Clinical neuropharmacology, 2000Co-Authors: Lance A. Smith, Michael G Jackson, Céline Bonhomme, Claire Chezaubernard, Ronald K. B. Pearce, Peter JennerAbstract:The ability of transdermal administration of the dopamine D2/D3 agonist Piribedil (1-[3,4-methylenedioxybenzyl)]-4-[(2-pyrimidinyl)]piperazine) to reverse hypokinesia and other motor deficits observed in MPTP-treated common marmosets was investigated. Piribedil (2.5-10.0 mg/animal), applied directly to the skin of the abdomen as a paste, produced a long-lasting and concentration-dependent reversal of motor deficits. The antiparkinsonian actions of Piribedil occurred within 10 minutes of drug administration and lasted as long as 10 hours. Transdermally applied Piribedil produced a pattern of locomotor activity characteristic of normal motor behavior in this species. Symptoms of nausea (marked excessive salivation, retching, and/or vomiting) were not observed after transdermal application of Piribedil. Additionally, pretreatment with the peripheral dopamine antagonist domperidone enhanced the antiparkinsonian effects of Piribedil. Application to the skin of monolayer or bilayer patches impregnated with Piribedil also produced a marked increase in locomotor activity and reversal of motor deficits. After application of various patch fractions (whole, one-half, or one-fourth), the increase in locomotor activity and reversal of disability correlated well with the surface area of skin covered. Measurement of serum levels of Piribedil after single application of bilayer patches showed a positive relationship between drug levels and antiparkinsonian activity. Repeated daily application of Piribedil bilayer patches for 5 days to MPTP-treated common marmosets primed to show dyskinesia by previous exposure to L-Dopa produced antiparkinsonian activity accompanied by dyskinetic movements. Transdermal administration of dopamine agonists such as Piribedil may provide a useful means of producing a long-lasting reversal of motor deficits in Parkinson's disease while avoiding acute adverse effects such as nausea.
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An appraisal of the antiparkinsonian activity of Piribedil in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets.
Movement disorders : official journal of the Movement Disorder Society, 1996Co-Authors: Lance A. Smith, Peter Jenner, Maria De Salvia, C. David MarsdenAbstract:The D2 dopamine agonist Piribedil is not widely used in the treatment of Parkinson's disease because it was thought to be effective mainly on parkinsonian tremor and to produce a high incidence of peripheral side effects, particular nausea. In this study, we used 1–methyl–4–phenyl–1,2,3,6–tetrahydropyridine (MPTP)–treated primates to reevaluate the antiparkinsonian ability of Piribedil after its oral administration in the presence or absence of domperidone pretreatment. Adult common marmosets (Callithrix jacchus) were treated with the nigral toxin MPTP to induce a parkinsonian syndrome characterised primarily by brady kinesia and other motor deficits. Oral administration of a solution of Piribedil [1–(3,4–methylenedioxybenzyl)–4–(2–pyrimidinyl) piperazine] produced a dose–related reversal of all MPTP locomotor and behavioural deficits. However, this effect was short lived and associated with unwanted effects, particular nausea and retching, which clearly hindered locomotion. In contrast, after pretreatment with the peripheral dopamine antagonist domperidone, administration of Piribedil did not induce nausea or retching in MPTP-treated marmosets. In these animals, Piribedil caused a more marked and and longer lasting enhancement of locomotor activity and a further reduction in behavioural deficits than that observed after administration of Piribedil alone. In addition, Piribedil induced increased vigilance and awareness. These data show that Piribedil can reverse akinesia and rigidity in MPTP-treated primates. In addition, they show the drug to be effective without peripheral side effects when used in conjuction with domperidone. These data indicate that Piribedil should be an effective monotherapy for Parkinson's disease.
Olivier Rascol - One of the best experts on this subject based on the ideXlab platform.
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Piribedil for the Treatment of Motor and Non-motor Symptoms of Parkinson Disease
CNS Drugs, 2016Co-Authors: Santiago Perez-lloret, Olivier RascolAbstract:Dopamine agonists are well-established symptomatic medications for treating early and advanced Parkinson disease (PD). Piribedil was one of the first agonists to be marketed (1969) and is widely used as an extended-release oral formulation in European, Latin-American, and Asian countries. Piribedil acts as a non-ergot partial dopamine D_2/D_3-selective agonist, blocks alpha2-adrenoreceptors and has minimal effects on serotoninergic, cholinergic, and histaminergic receptors. Animal models support the efficacy of Piribedil to improve parkinsonian motor symptoms with a lower propensity than levodopa to induce dyskinesia. In PD patients, randomized double-blind studies show that Piribedil (150–300 mg/day, three times daily) is superior to placebo in improving motor disability in early PD patients. Based on such evidence, Piribedil was considered in the last Movement Disorder Society Evidence-Based Medicine review as “efficacious” and “clinically useful” for the symptomatic treatment of PD, either as monotherapy or in conjunction with levodopa, in non-fluctuating early PD patients. This effect appears comparable to what is known from other D_2 agonists. However, randomized controlled trials are not available to assess the effect of Piribedil in managing levodopa-induced motor complications. Pilot clinical studies suggest that Piribedil may improve non-motor symptoms, such as apathy, but confirmatory trials are needed. The tolerability and safety profile of Piribedil fits with that of the class of dopaminergic agonists. As for other non-ergot agonists, pneumo-pulmonary, retroperitoneal, and valvular fibrotic side effects are not a concern with Piribedil. The original combination of Piribedil D_2 dopaminergic and alpha-2 adrenergic properties deserve further investigations to better understand its antiparkinsonian profile.
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Early Piribedil monotherapy of Parkinson's disease: A planned seven-month report of the REGAIN study.
Movement disorders : official journal of the Movement Disorder Society, 2006Co-Authors: Olivier Rascol, Bruno Dubois, Alexandre Castro Caldas, Stephen Senn, Susanna Del Signore, Andrew J. LeesAbstract:Piribedil is a D-2 dopamine agonist, which has been shown to improve symptoms of Parkinson's disease (PD) when combined with L-dopa. The objective of this study was to compare the efficacy of Piribedil monotherapy to placebo in patients with early PD over a 7-month period. Four hundred and five earl PD patients were randomized (double-blind) to Piribedil (150-300 mg/day) or placebo. L-dopa open-label supplementation was permitted. Unified Parkinson Disease Rating Scale part III (UPDRS III) score as the last observation on monotherapy over 7 months was the primary outcome measure. Secondary outcomes were proportion of responders (UPDRS III improvement > 30%), patients remaining on monotherapy after 7 months, UPDRS III subscores, and UPDRS II. UPDRS III improved on Piribedil (-4.9 points) versus a worsening on placebo (2.6 points; estimated effect = 7.26 points; 95% Cl = 5.38-9.14; P < 0.0001). The proportion of responders was significantly higher for Piribedil (42%) than for placebo (14%) (OR = 4.69; 95% CI = 2.82-7.80; P < 0.001). Piribedil significantly improved several UPDRS III subscores. UPDRS II improved on Piribedil by -1.2 points, while it deteriorated by 1.5 points on placebo (estimated effect = 2.71; 95% CI = 1.8-3.62; P < 0.0001). The proportion of patients remaining on monotherapy after 7 months was greater in the Piribedil group (OR = 3.72; 95% CI = 2.26-6.11; P < 0.001). Safety was consistent with that reported for other dopamine agonists, gastrointestinal side effects being the most common (22% of patients in Piribedil group vs. 14% on placebo). Piribedil is effective and safe as early PD therapy. (C) 2006 Movement Disorder Society.
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Efficacy of Piribedil as early combination to levodopa in patients with stable Parkinson's disease: a 6-month, randomized, placebo-controlled study.
Movement disorders : official journal of the Movement Disorder Society, 2003Co-Authors: Marc Ziegler, Susanna Del Signore, Alexandre Castro-caldas, Olivier RascolAbstract:Piribedil is a non-ergot D2/D3 agonist with a significant antagonist action on α2A and α2C adrenergic receptor subtypes. This double-blind placebo-controlled study was undertaken to confirm the efficacy of 150 mg/day Piribedil po in improving motor symptoms of idiopathic Parkinson's disease (PD) in nonfluctuating patients insufficiently controlled by a stable daily dose of levodopa (L-dopa). Efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) III score as primary criterion over 4 months. A second comparison was planned at 6 months, after possible adjustment of L-dopa. At 4 months, the rate of response, defined as a 30% decrease from baseline on UPDRS III score, was significantly greater with Piribedil compared with placebo (56.4% vs. 37.7%; P = 0.040). At 6 months, the better efficacy of Piribedil was maintained (61.8% of responders vs. 39.6% on placebo; P = 0.020). The difference between groups on UPDRS III change from baseline reached statistical significance only at 6 months: −10.0 points in the Piribedil group vs. −6.7 points in the placebo group (P = 0.037). Secondary end-points were not significantly different. The most frequently reported adverse events were gastrointestinal symptoms (27 of 61 patients in the Piribedil group vs. 13 of 54 patients in the placebo group). In conclusion, a 6-month oral administration of 150 mg/day Piribedil in combination with L-dopa is well tolerated, except for minor gastrointestinal symptoms at the beginning of the treatment and significantly improves motor symptoms compared with placebo in PD nonfluctuating patients. © 2003 Movement Disorder Society
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A randomized, double-blind study of a skin patch of a dopaminergic agonist, Piribedil, in Parkinson's disease.
Movement disorders : official journal of the Movement Disorder Society, 1999Co-Authors: Jean-louis Montastruc, Olivier Rascol, Marc Ziegler, Muriel MalbezinAbstract:This randomized, double-blind trial was designed to evaluate the efficacy of a transdermal system of Piribedil on the motor symptoms of Parkinson's disease during 3 weeks of treatment administered to three different groups: placebo, one Piribedil patch (1 PP), and two (2 PP) Piribedil patches. Twenty-seven patients with idiopathic Parkinson's disease, treated with L-dopa but not sufficiently controlled, were included in this trial. The test treatment did not demonstrate any clinical efficacy on either the main end point (Unified Parkinson's Disease Rating Scale motor score) or the secondary end points (rigidity, bradykinesia, postural, and resting tremor scores). The main adverse events were nausea (11%), vomiting (7.4%), and malaise (7.4%) mainly observed in the placebo group (four of seven patients). The local acceptability of the transdermal system was good. Plasma Piribedil concentrations at the end of treatment were 6.74 ± 1.10 and 9.31 ± 3.33 ng/mL in the 1 PP and 2 PP groups, respectively. These plasma levels could account for the lack of clinical efficacy, because a previous pharmacokinetics-PD study conducted in parkinsonian patients and treated with the intravenous route demonstrated that the critical limits of activity on tremor were between 10 and 30 ng/mL.