Pramipexole is a dopamine agonist used in the treatment of Parkinson’s disease and Restless legs syndrome. Although off-label, the use of Pramipexole as an adjunct therapy in treatment resistant depression has recent...Pramipexole is a dopamine agonist used in the treatment of Parkinson’s disease and Restless legs syndrome. Although off-label, the use of Pramipexole as an adjunct therapy in treatment resistant depression has recently been documented in the literature with promising results. We present a 75-year-old male with MDD who has failed trials of SSRIs, SNRIs, TCAs, SGA, TMS, Ketamine, and ECT who was initiated on Pramipexole. We discuss, based on existing literature, the probability of a favorable long-term response to Pramipexole and the potential side effects for our patient. We also highlight the need for future studies designed to test the efficacy of Pramipexole in geriatric patients with TRD.展开更多
Background: Apathy occurs frequently in patients with Parkinson’s disease (PD), and has a negative impact on activities of daily living through loss of motivation. Pramipexole (PPX), which shows preferential affinity...Background: Apathy occurs frequently in patients with Parkinson’s disease (PD), and has a negative impact on activities of daily living through loss of motivation. Pramipexole (PPX), which shows preferential affinity for D3 dopamine receptor in the mesolimbic system, is thought to influence mood and motivation. Therefore, we conducted an open-label case-control study to examine the effect of PPX on apathy in PD. Methods: We studied 36 PD patients (mean age, 70.4 ± 8.1 years), who had been treated only with L-DOPA. PPX was added to L-DOPA treatment in 24 patients (PPX group) and other 12 patients continued with L-DOPA alone (non-PPX group). The study period was 8 weeks. Apathy was assessed using the revised apathy scale for Japanese. Motor function was assessed with part III of the Unified Parkinson’s Disease Rating Scale (UPDRS). Results: Seventeen of 36 patients (47%) were diagnosed as having apathy. In the PPX group, apathy scale significantly improved from 17.3 to 13.8 at week 8 (p < 0.05). Motor function also improved significantly from 16.1 to 7.6 at week 8 (p < 0.0001). In the non-PPX group, apathy scale and UPDRS both showed no change during the study period. There was no correlation between changes in apathy scale and UPDRS in either the PPX or non-PPX group. Conclusion: PPX may be effective for treating apathy as well as motor dysfunction in PD.展开更多
Fibromyalgia(FM) is a complex pathology described as persistent hyperalgesia including somatic and mood dysfunctions, depression and anxiety. Although the etiology of FM is still unknown, a significant decrease in bio...Fibromyalgia(FM) is a complex pathology described as persistent hyperalgesia including somatic and mood dysfunctions, depression and anxiety. Although the etiology of FM is still unknown, a significant decrease in biogenic amines is a common characteristic in its pathogenesis. Here, our main objective was to investigate the role of dopamine D3/D2 receptor during the reserpine-induced pain in mice. Our results showed that pramipexole(PPX) – a dopaminergic D3/D2 receptor agonist – inhibited mechanical allodynia and thermal sensitivity induced by reserpine. Relevantly, PPX treatment decreased immobility time and increased the number of grooming in the forced swimming test and splash test, respectively. Animals that received PPX remained longer in the open arms than the reserpine group using elevated plusmaze apparatus. The repeated PPX administration, given daily for 4 days, significantly blocked the mechanical and thermal allodynia during FM model, similarly to pregabalin, although it failed to affect the reserpine-induced thermal nociception. Reserpine administration induced significant downregulation of dopamine concentration in the central nervous system, and repeated treatment with PPX restored dopamine levels in the frontal cortex and spinal cord tissues. Moreover, PPX treatment inhibited oxidants production such as DCFH(2′,7′-dichlorodihydrofluorescein) and nitrite, also decreased oxidative damage(carbonyl), and upregulated the activity of superoxide dismutase in the spinal cord. Together, our findings demonstrated the ability of dopamine D3/D2 receptor-preferring agonist in reducing pain and mood dysfunction allied to FM in mice. All experimental protocols were approved by the Universidade Federal de Santa Catarina(UFSC) Ethics Committee(approval No. 2572210218) on May 10, 2018.展开更多
A randomized, double blind, and active reference-controlled study was carried out among 116 patients suffering from idiopathic Parkinson’s disease (PD). The aim of the study was to compare the safety and efficacy of ...A randomized, double blind, and active reference-controlled study was carried out among 116 patients suffering from idiopathic Parkinson’s disease (PD). The aim of the study was to compare the safety and efficacy of alpha-dihydroergocryptine (DHEC) vs. pramipexole (PRAM) as an adjunct symptomatic therapy to levodopa in PD patients. The motor symptoms, assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) III subscale, was identified as efficacy target. Fifty-six patients were randomized to DHEC and 60 to PRAM. Patients included were under constant levodopa dose for at least 3 months before entering the study, with baseline UPDRS III ≥14. They underwent a 16-week treatment. Out of the 116 included patients, 85 (39 in DHEC group and 46 in PRAM group, respectively) completed the study protocol. In DHEC group, UPDRS III decreased by 24.2% from baseline at week 10 and by 28.1% at week 16. In PRAM group, UPDRS III decreased by 27.1% from baseline at week 10 and by 29.2% at week 16. The data were highly significant展开更多
Background: Drug adherence decreased in patients with Parkinson’ s disease (PD) because of taking many different types of drugs. We evaluated drug adherence after switching from immediate-release (IR) to once-daily e...Background: Drug adherence decreased in patients with Parkinson’ s disease (PD) because of taking many different types of drugs. We evaluated drug adherence after switching from immediate-release (IR) to once-daily extended-release (ER) pramipexole (PPX) in PD. Methods: This study included 35 PD patients (20 men, 15 women);10 were taking oral PPX alone, and 25 were also using another anti-PD drug. PPX-IR was switched overnight to PPX-ER without gradual tapering. One month after switching, improvement in timing adherence and reduction in medication burden were evaluated by a questionnaire using a visual analog scale (VAS) (0: No change;10: Better). Motor function was assessed using part III of the Unified Parkinson’s Disease Rating Scale (UPDRS). Results: The VAS score for improvement in timing adherence was 8.1 ± 0.5 (mean ± standard error), and that for reduction in medication burden was 7.3 ± 0.6. There was a significant negative correlation (ρ = -0.43, p = 0.01) between the VAS score and number of types of medications. The UPDRS part III score improved significantly after switching展开更多
Parkinson’s disease is a common condition usually treated by dopaminergic agents and many behavioral abnormalities such as impulse control disorders (ICD) are connected with that usage. Pathological gambling, a form ...Parkinson’s disease is a common condition usually treated by dopaminergic agents and many behavioral abnormalities such as impulse control disorders (ICD) are connected with that usage. Pathological gambling, a form of ICD includes is a clinical condition that disrupts personal, family and occupational activity. Pramipexole a D2 AND D3 agonist may be associated with pathological gambling. We present a case of 74-year-old male patient who was diagnosed with Parkinson’s disease (PD). His doctor advised him to take pramipexole 0.18 mg/p.o./day. A month after the onset of treatment he manifested a behavior of pathological gambling. After the discontinuation of the drug all this behavior was interrupted.展开更多
Pramipexole belongs to a class of nonergot dopamine agonist recently approved for the treatment of early and advanced Parkinson's disease.A validated specific stability indicating reversed-phase liquid chromatogra...Pramipexole belongs to a class of nonergot dopamine agonist recently approved for the treatment of early and advanced Parkinson's disease.A validated specific stability indicating reversed-phase liquid chromatographic method has been developed for the quantitative determination of pramipexole in bulk as well as in pharmaceutical dosage forms in the presence of degradation products.Forced degradation studies were performed by exposition of drug to hydrolytic(acidic and basic),oxidative and photolytic stress conditions,as defined under ICH guideline Q1A(R2).Significant degradation was observed under hydrolytic,oxidative and photolytic conditions and the degradation products formed were identified by LC-MS.展开更多
Objective:To evaluate the non-inferiority of pramipexole extended-release(ER)versus immediate-release(IR)in Chinese patients with Parkinson’s disease(PD)in a double-blind,randomized,parallel-group study.Methods:Subje...Objective:To evaluate the non-inferiority of pramipexole extended-release(ER)versus immediate-release(IR)in Chinese patients with Parkinson’s disease(PD)in a double-blind,randomized,parallel-group study.Methods:Subjects were Chinese patients with idiopathic PD with diagnosis≥2 years prior to trial,age≥30 years old at diagnosis,and Modified Hoehn and Yahr score 2-4 during‘on’-time.Subjects received treatment with pramipexole ER(n=234)or IR(n=239).Non-inferiority was based on the primary endpoint,the change from baseline to end of maintenance(week 18)in the UPDRS(Parts II+III)total score.Results:For the primary endpoint,the adjusted mean changes(standard error)of UPDRS Parts II+III at week 18 were−13.81(0.655)and−13.05(0.643)for ER and IR formulations,respectively,using ANCOVA adjusted for treatment and centre(fixed effect)and baseline(covariate).The adjusted mean between group difference was 0.8 for the 2-sided 95%CI(−1.047,2.566).Since the lower limit of the 2-sided 95%CI(−1.047)for treatment difference was higher than the non-inferiority margin of−4,non-inferiority between pramipexole ER and IR was demonstrated.The incidence of adverse events(AEs)was 68.8%in the ER arm and 73.6%in the IR arm with few severe AEs(ER:2.1%;IR:3.8%).Conclusion:Based on the UPDRS II+III score,pramipexole ER was non-inferior to pramipexole IR.The safety profiles of pramipexole ER and IR were similar.These results were based on comparable mean daily doses and durations of treatment for both formulations.展开更多
文摘Pramipexole is a dopamine agonist used in the treatment of Parkinson’s disease and Restless legs syndrome. Although off-label, the use of Pramipexole as an adjunct therapy in treatment resistant depression has recently been documented in the literature with promising results. We present a 75-year-old male with MDD who has failed trials of SSRIs, SNRIs, TCAs, SGA, TMS, Ketamine, and ECT who was initiated on Pramipexole. We discuss, based on existing literature, the probability of a favorable long-term response to Pramipexole and the potential side effects for our patient. We also highlight the need for future studies designed to test the efficacy of Pramipexole in geriatric patients with TRD.
文摘Background: Apathy occurs frequently in patients with Parkinson’s disease (PD), and has a negative impact on activities of daily living through loss of motivation. Pramipexole (PPX), which shows preferential affinity for D3 dopamine receptor in the mesolimbic system, is thought to influence mood and motivation. Therefore, we conducted an open-label case-control study to examine the effect of PPX on apathy in PD. Methods: We studied 36 PD patients (mean age, 70.4 ± 8.1 years), who had been treated only with L-DOPA. PPX was added to L-DOPA treatment in 24 patients (PPX group) and other 12 patients continued with L-DOPA alone (non-PPX group). The study period was 8 weeks. Apathy was assessed using the revised apathy scale for Japanese. Motor function was assessed with part III of the Unified Parkinson’s Disease Rating Scale (UPDRS). Results: Seventeen of 36 patients (47%) were diagnosed as having apathy. In the PPX group, apathy scale significantly improved from 17.3 to 13.8 at week 8 (p < 0.05). Motor function also improved significantly from 16.1 to 7.6 at week 8 (p < 0.0001). In the non-PPX group, apathy scale and UPDRS both showed no change during the study period. There was no correlation between changes in apathy scale and UPDRS in either the PPX or non-PPX group. Conclusion: PPX may be effective for treating apathy as well as motor dysfunction in PD.
基金supported by grants from Programa de Pos-graduacao em Neurociencias(PGN),Programa INCT-INOVAMED(grant No.465430/2014-7)Fundacao de Apoio à Pesquisa e Inovacao do Estado de Santa Catarina(FAPESC)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior(CAPES)。
文摘Fibromyalgia(FM) is a complex pathology described as persistent hyperalgesia including somatic and mood dysfunctions, depression and anxiety. Although the etiology of FM is still unknown, a significant decrease in biogenic amines is a common characteristic in its pathogenesis. Here, our main objective was to investigate the role of dopamine D3/D2 receptor during the reserpine-induced pain in mice. Our results showed that pramipexole(PPX) – a dopaminergic D3/D2 receptor agonist – inhibited mechanical allodynia and thermal sensitivity induced by reserpine. Relevantly, PPX treatment decreased immobility time and increased the number of grooming in the forced swimming test and splash test, respectively. Animals that received PPX remained longer in the open arms than the reserpine group using elevated plusmaze apparatus. The repeated PPX administration, given daily for 4 days, significantly blocked the mechanical and thermal allodynia during FM model, similarly to pregabalin, although it failed to affect the reserpine-induced thermal nociception. Reserpine administration induced significant downregulation of dopamine concentration in the central nervous system, and repeated treatment with PPX restored dopamine levels in the frontal cortex and spinal cord tissues. Moreover, PPX treatment inhibited oxidants production such as DCFH(2′,7′-dichlorodihydrofluorescein) and nitrite, also decreased oxidative damage(carbonyl), and upregulated the activity of superoxide dismutase in the spinal cord. Together, our findings demonstrated the ability of dopamine D3/D2 receptor-preferring agonist in reducing pain and mood dysfunction allied to FM in mice. All experimental protocols were approved by the Universidade Federal de Santa Catarina(UFSC) Ethics Committee(approval No. 2572210218) on May 10, 2018.
文摘A randomized, double blind, and active reference-controlled study was carried out among 116 patients suffering from idiopathic Parkinson’s disease (PD). The aim of the study was to compare the safety and efficacy of alpha-dihydroergocryptine (DHEC) vs. pramipexole (PRAM) as an adjunct symptomatic therapy to levodopa in PD patients. The motor symptoms, assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) III subscale, was identified as efficacy target. Fifty-six patients were randomized to DHEC and 60 to PRAM. Patients included were under constant levodopa dose for at least 3 months before entering the study, with baseline UPDRS III ≥14. They underwent a 16-week treatment. Out of the 116 included patients, 85 (39 in DHEC group and 46 in PRAM group, respectively) completed the study protocol. In DHEC group, UPDRS III decreased by 24.2% from baseline at week 10 and by 28.1% at week 16. In PRAM group, UPDRS III decreased by 27.1% from baseline at week 10 and by 29.2% at week 16. The data were highly significant
文摘Background: Drug adherence decreased in patients with Parkinson’ s disease (PD) because of taking many different types of drugs. We evaluated drug adherence after switching from immediate-release (IR) to once-daily extended-release (ER) pramipexole (PPX) in PD. Methods: This study included 35 PD patients (20 men, 15 women);10 were taking oral PPX alone, and 25 were also using another anti-PD drug. PPX-IR was switched overnight to PPX-ER without gradual tapering. One month after switching, improvement in timing adherence and reduction in medication burden were evaluated by a questionnaire using a visual analog scale (VAS) (0: No change;10: Better). Motor function was assessed using part III of the Unified Parkinson’s Disease Rating Scale (UPDRS). Results: The VAS score for improvement in timing adherence was 8.1 ± 0.5 (mean ± standard error), and that for reduction in medication burden was 7.3 ± 0.6. There was a significant negative correlation (ρ = -0.43, p = 0.01) between the VAS score and number of types of medications. The UPDRS part III score improved significantly after switching
文摘Parkinson’s disease is a common condition usually treated by dopaminergic agents and many behavioral abnormalities such as impulse control disorders (ICD) are connected with that usage. Pathological gambling, a form of ICD includes is a clinical condition that disrupts personal, family and occupational activity. Pramipexole a D2 AND D3 agonist may be associated with pathological gambling. We present a case of 74-year-old male patient who was diagnosed with Parkinson’s disease (PD). His doctor advised him to take pramipexole 0.18 mg/p.o./day. A month after the onset of treatment he manifested a behavior of pathological gambling. After the discontinuation of the drug all this behavior was interrupted.
文摘Pramipexole belongs to a class of nonergot dopamine agonist recently approved for the treatment of early and advanced Parkinson's disease.A validated specific stability indicating reversed-phase liquid chromatographic method has been developed for the quantitative determination of pramipexole in bulk as well as in pharmaceutical dosage forms in the presence of degradation products.Forced degradation studies were performed by exposition of drug to hydrolytic(acidic and basic),oxidative and photolytic stress conditions,as defined under ICH guideline Q1A(R2).Significant degradation was observed under hydrolytic,oxidative and photolytic conditions and the degradation products formed were identified by LC-MS.
基金Boehringer lngelheim lnternational GmbH sponsored this study.
文摘Objective:To evaluate the non-inferiority of pramipexole extended-release(ER)versus immediate-release(IR)in Chinese patients with Parkinson’s disease(PD)in a double-blind,randomized,parallel-group study.Methods:Subjects were Chinese patients with idiopathic PD with diagnosis≥2 years prior to trial,age≥30 years old at diagnosis,and Modified Hoehn and Yahr score 2-4 during‘on’-time.Subjects received treatment with pramipexole ER(n=234)or IR(n=239).Non-inferiority was based on the primary endpoint,the change from baseline to end of maintenance(week 18)in the UPDRS(Parts II+III)total score.Results:For the primary endpoint,the adjusted mean changes(standard error)of UPDRS Parts II+III at week 18 were−13.81(0.655)and−13.05(0.643)for ER and IR formulations,respectively,using ANCOVA adjusted for treatment and centre(fixed effect)and baseline(covariate).The adjusted mean between group difference was 0.8 for the 2-sided 95%CI(−1.047,2.566).Since the lower limit of the 2-sided 95%CI(−1.047)for treatment difference was higher than the non-inferiority margin of−4,non-inferiority between pramipexole ER and IR was demonstrated.The incidence of adverse events(AEs)was 68.8%in the ER arm and 73.6%in the IR arm with few severe AEs(ER:2.1%;IR:3.8%).Conclusion:Based on the UPDRS II+III score,pramipexole ER was non-inferior to pramipexole IR.The safety profiles of pramipexole ER and IR were similar.These results were based on comparable mean daily doses and durations of treatment for both formulations.
