Effects Of Rotigotine Research Articles

Effect of rotigotine on the quality of emergence from general anesthesia in patients undergoing deep brain stimulation

Objective: To investigate the effect of rotigotine on the quality of emergence from general anesthesia in patients undergoing deep brain stimulation (DBS). Methods: A total of 42 patients (31 males and 11 females, aged 55-85 years) undergoing DBS surgery under general anesthesia in the First Affiliated Hospital of Zhengzhou University from March 2020 to October 2021 were selected. The patients were divided into non-rotigotine group (n=21) and rotigotine group (n=21) by using a random number table according to whether rotigotine patch was used. Postoperative recovery time, extubation time, length of postanesthesia care unit (PACU) stay, and grades of muscle tension, swallowing function and salivary secretion during recovery were compared between the two groups. Meanwhile, the incidence of adverse events during extubation was also compared. Results: The postoperative recovery time, extubation time and length of PACU stay in rotigotine group were (20.3±2.6) min, (30.6±3.1) min and (46.4±3.9) min, respectively, which were shorter than those of non-rotigotine group [(29.0±5.8) min, (42.6±10.0) min and (63.0±18.9) min, respectively] (all P<0.05). The grades of postoperative muscle tension, swallowing function and salivary secretion in rotigotine group [M(Q1, Q3)] were 1(1, 2), 1(1, 2) and 1(1, 1), respectively, which were lower than those of non-rotigotine group [2(2, 3), 2(2, 2) and 2(1, 2), respectively] (P=0.001, 0.002 and 0.011). The incidence of adverse events during anesthesia extubation in rotigotine group was 14.3% (3/21), which was lower than that of non-rotigotine group [42.9% (9/21), P=0.040]. Conclusion: Rotigotin patch is helpful to improve the quality of emergence from general anesthesia in patients undergoing DBS and reduce the occurrence of adverse events during extubation.

Rotigotine protects against oxidized low-density lipoprotein(ox-LDL)-induced damages in human umbilical vein endothelial cells(HUVECs)

ABSTRACT Rotigotine is a non-ergoline dopamine agonist that has been licensed for the treatment of Parkinson’s disease. Cardiovascular diseases are the world’s leading cause of death. Ox-LDL- induced endothelial damages are involved in the initiation and progression of cardiovascular diseases. In this study, we assessed the beneficial properties of Rotigotine on ox-LDL-induced insults to HUVECs to highlight its potential use in the treatment of cardiovascular diseases. Our findings show that Rotigotine suppresses the expressions of low-density lipoprotein receptor (LDL-R), proprotein convertase subtilisin/kexin type 9 (PCSK-9), and sterol regulatory element-binding protein (SREBP-2). It also inhibits ox-LDL-induced cholesterol accumulation in endothelial cells (ECs), improves U937 monocytes adhesion, and decreases the representation of NADPH oxidase (NOX-4) and generation of reactive oxygen species (ROS) in endothelial cells (ECs). Furthermore, Rotigotine inhibited the expressions of both vascular cellular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HUVECs and had anti-inflammatory efficacy in ox-LDL-induced cells by inhibiting the expressions of pro-inflammatory cytokines. Notably, Rotigotine inhibits the activation of nuclear factor-kappaB (NF-κB) by preventing nuclear translocation of NF-κB p65 and reducing the luciferase activity of NF-κB reporter. We, therefore, conclude that these effects of Rotigotine on HUVECs suggest that it may play a therapeutic role in cardiovascular diseases.

Lipopolysaccharide/D-galactosamine-induced acute liver injury could be attenuated by dopamine receptor agonist rotigotine via regulating NF-κB signaling pathway

The pathological of lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute liver injury is similar to what is seen clinically, and be mediated by the release of pro-inflammatory mediators. A growing body of studies have shown that dopamine (DA) and DA receptor agonist are associated with inflammation and immune response. Rotigotine, a non-ergoline dopamine receptor agonist, is a drug for the treatment of Parkinson’s disease. Rotigotine-loaded microspheres (RoMS) is an intramuscular extended-release agent, which can steadily release rotigotine for more than 7 days after a single administration. The present study aimed to investigate the effects of rotigotine and RoMS on inflammation and acute liver injury induced by LPS/D-Gal in mice. The LPS/D-Gal-induced liver injury was evidenced by increases of serum aminotransferases activities and liver histological lesions. Pretreatment with rotigotine or RoMS not only ameliorated the liver histologic lesions, but also reduced the activities of serum aminotransferases and the production of TNF-α. It also showed that rotigotine and RoMS increased DA receptor 2 (DRD2) expression in LPS/D-Gal-exposed mice. Rotigotine and RoMS activated β-arrestin 2, inhibited the phosphorylation of Akt, IκB and the transposition of NF-κB. In line with the above findings, the protective effects of rotigotine and RoMS were abrogated by haloperidol, a DA receptor antagonist. In conclusion, dopamine receptor agonist can regulate NF-κB inflammatory signaling pathway and exert protective effects in LPS/D-Gal-induced liver injury.

Rotigotine Transdermal Patch for Motor and Non-motor Parkinson's Disease: A Review of 12 Years' Clinical Experience.

Motor and non-motor symptoms (NMS) have a substantial effect on the health-related quality of life (QoL) of patients with Parkinson's disease (PD). Transdermal therapy has emerged as a time-tested practical treatment option, and the rotigotine patch has been used worldwide as an alternative to conventional oral treatment for PD. The efficacy of rotigotine on motor aspects of PD, as well as its safety and tolerability profile, are well-established, whereas its effects on a wide range of NMS have been described and studied but are not widely appreciated. In this review, we present our overall experience with rotigotine and its tolerability and make recommendations for its use in PD and restless legs syndrome, with a specific focus on NMS, underpinned by level 1–4 evidence. We believe that the effective use of the rotigotine transdermal patch can address motor symptoms and a wide range of NMS, improving health-related QoL for patients with PD. More specifically, the positive effects of rotigotine on non-motor fluctuations are also relevant. We also discuss the additional advantages of the transdermal application of rotigotine when oral therapy cannot be used, for instance in acute medical emergencies or nil-by-mouth or pre/post-surgical scenarios. We highlight evidence to support the use of rotigotine in selected cases (in addition to general use for motor benefit) in the context of personalised medicine.

Rotigotine protects dopaminergic neurons through dopamine D2 receptor against 6-hydroxydopamine

Dopamine (DA) receptor (D1 and D2-like receptors) agonists are known to affect expression levels of DA receptors. Rotigotine, a DA D2-like receptor agonist, has been developed for treating Parkinson’s disease (PD). However, its role in PD by acting through DA D2-like receptors has not been fully understood yet. The purpose of this study was to investigate neuroprotective effects of rotigotine through DA D2 and D3 receptors in 6-hydroxydopamine (6-OHDA) induced mouse model of PD. Expression level of tyrosine hydroxylase (TH) was examined using immunohistochemistry and Western blot analysis. Results revealed that unilateral injection of 6-OHDA into the midbrain caused significant loss of TH positive cells in the substantia nigra, whereas rotigotine inhibited such loss of TH cells in 6-OHDA-induced mouse model of PD. In vitro experiments demonstrated that rotigotine increased expression levels of TH against 6-OHDA-induced toxicity. The expression level of TH after treatment with L’741,626, a D2 receptor antagonist was decreased more than that after treatment with GR 103691, a D3 receptor antagonist. These results suggest that rotigotine can protect DA neurons against 6-OHDA induced toxicity and that the protective effect of rotigotine for DAergic neurons through a DA D2 receptor is stronger than that through a DA D3 receptor.

A randomized controlled double-blind study of rotigotine on neuropsychiatric symptoms in de novo PD

Management of apathy, depression and anxiety in Parkinson’s disease (PD) represents a challenge. Dopamine agonists have been suggested to be effective. This multicenter, randomized (1:1), double-blind study assessed the 6-month effect of rotigotine versus placebo on apathy, depression and anxiety in de novo PD. The primary outcome was the change of apathy, measured with the LARS. The secondary outcomes were the change in depression and anxiety, measured with BDI-2 and STAI-trait and state. Forty-eight drug-naive PD patients were included. The primary outcome was not reached, with a surprisingly high placebo effect on apathy (60%). There was no significant difference in the change of depression at 6 months between rotigotine and placebo. Trait-anxiety was significantly improved by rotigotine compared to placebo (p = 0.04). Compared to placebo, low dose rotigotine significantly improved trait anxiety, but not apathy and depression. The major placebo effect on apathy points towards the importance of a multidisciplinary and tight follow-up in the management of neuropsychiatric symptoms.

Real-world safety and effectiveness of rotigotine in patients with Parkinson’s disease: analysis of a post-marketing surveillance study in Japan

Objective The aim of this study was to evaluate the safety and effectiveness of rotigotine under daily clinical practice in Parkinson’s disease patients. Methods The study was a prospective, non-interventional, observational study targeting patients who were treated with rotigotine for the first time, with a 1-year follow-up period from September 2013 to August 2016. Results There were 603 patients in the safety population and 599 patients in the effectiveness population. The mean age was 71.6 years, and the age group of ≥65 and ≥80 years accounted for 80% and 18.6% of all patients, respectively. The frequency of adverse drug reaction (ADR) was 34.3%, and common ADRs were application site reaction (20.2%), typical for transdermal patches. However, the majority of patients recovered or was recovering from these ADRs and were non-serious. Although ADRs related to non-motor symptoms of Parkinson’s disease were observed, most of them were non-serious. Total scores of the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) (ON-time) significantly decreased from baseline in the effectiveness population. In the analysis of overall improvement in 12 months of post-treatment, ≥70% of patients achieved mild or greater improvement. The safety profiles and improvements in the UPDRS-III score were similar in both the ≥80 years of age group and younger age group. Conclusion There were no new or notable safety concerns observed, and the effectiveness of rotigotine was suggested in daily clinical practice.

Effects of the rotigotine and venlafaxine on sexual dysfunction and depression in rats

Introduction: Rationale Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI), differing from the selective serotonin reuptake inhibitors (SSRIs) in that it inhibits the reuptake of both serotonin and norepinephrine. Reportedly, the rates of sexual dysfunction with venlafaxine are lower or similar to those of the SSRIs. Dopamine plays a role in sexual behavior and is related to ejaculation. Objectives: To assess changes in the potential effects of dopamine receptor agonist rotigotine on venlafaxine -induced sexual dysfunction and depression in rats. Methods: The depressive-like rats models induced by olfactory bulbectomy (OB) were intragastrically administered with venlafaxine (40 mg/kg) and co-administered with rotigotine or rotigotine-loaded microspheres (RoMS) at dose of 20 mg/kg. The sex function and anti-depressive effects were observed by copulatory behavior test (CBT) and open field test (OFT) respectively. Result: The olfactory bulbectomy induced sexual dysfunction which significantly deteriorated by venlafaxine administration. Rotigotine could not attenuate the venlafaxine-induced sexual dysfunction, but RoMS could do it partly. The venlafaxine showed anti-depressive efficacy of OB, but the RoMS could not do better. Conclusion: RoMS partly reverses the venlafaxine-induced sexual dysfunction. It may be better that patients with depression are co-administered with venlafaxine and RoMS.

Dopaminergic neuroprotective effects of rotigotine via 5-HT1A receptors: Possibly involvement of metallothionein expression in astrocytes

Astrocytes exert neuroprotective effects through production of antioxidant molecules and neurotrophic factors. A recent study showed that stimulation of astrocyte serotonin 1A (5-HT1A) receptors promotes astrocyte proliferation and upregulation of the antioxidant molecules metallothionein (MT)-1,2, which protect dopaminergic neurons against oxidative stress. Rotigotine, an anti-parkinsonian drug, can bind to dopamine and 5-HT1A receptors. In this study, we examined neuroprotective effects of rotigotine in models of Parkinson’s disease and involvement of astrocyte 5-HT1A receptors in neuroprotective effects of rotigotine against dopaminergic neurodegeneration. Rotigotine increased the number of astrocytes and MT-1,2 expression in cultured astrocytes. Pretreatment with conditioned media from rotigotine-treated astrocytes significantly inhibited 6-hydroxydopamine (6-OHDA)-induced dopaminergic neurotoxicity. These effects were completely blocked by a 5-HT1A antagonist or MT-1,2 specific antibody. Subcutaneous administration of rotigotine increased MT-1,2 expression in striatal astrocytes and prevented reduction of dopaminergic neurons in the substantia nigra of a 6-OHDA-lesioned mouse model of Parkinson’s disease. These effects were blocked by co-administration with a 5-HT1A antagonist. These results suggest that rotigotine exerts neuroprotective effects through upregulation of MT expression in astrocytes by targeting 5-HT1A receptors. Our findings provide a possible therapeutic application of rotigotine to prevent dopaminergic neurodegeneration in Parkinson’s disease.

Rotigotine suppresses sleep-related muscle activity augmented by injection of dialysis patients\u2019 sera in a mouse model of restless legs syndrome

Idiopathic restless legs syndrome (RLS) has a genetic basis wherein BTBD9 is associated with a higher risk of RLS. Hemodialysis patients also exhibit higher rates of RLS compared with the healthy population. However, little is known about the relationship of BTBD9 and end-stage renal disease to RLS pathophysiology. Here we evaluated sleep and leg muscle activity of Btbd9 mutant (MT) mice after administration of serum from patients with either idiopathic or RLS due to end-stage renal disease (renal RLS) and investigated the efficacy of treatment with the dopamine agonist rotigotine. At baseline, the amount of rapid eye movement (REM) sleep was decreased and leg muscle activity during non-REM (NREM) sleep was increased in MT mice compared to wild-type (WT) mice. Wake-promoting effects of rotigotine were attenuated by injection of serum from RLS patients in both WT and MT mice. Leg muscle activity during NREM sleep was increased only in MT mice injected with serum from RLS patients of ideiopatic and renal RLS. Subsequent treatment with rotigotine ameliorated this altered leg muscle activity. Together these results support previous reports showing a relationship between the Btbd9/dopamine system and RLS, and elucidate in part the pathophysiology of RLS.

Effects of rotigotine and rotigotine extended-release microsphere therapy on myocardial ischemic injury in mice

Rotigotine is a dopamine receptor agonist that can improve motor function in Parkinson's disease (PD) patients. Rotigotine extended-release microsphere (RoMS) is an extended-release intramuscular formulation that exhibits a sustained release of rotigotine over a 14-day period. The clinical trials of RoMS has been carried out in USA and China. The purpose of this study is to observe the effects of RoMS therapy on myocardial ischemic injury in mice, to know whether RoMS alleviate or deteriorate the myocardial ischemic injury while PD patient has onset of myocardial ischemia concurrent after administered with RoMS. A mouse model of myocardial ischemia was established using isoproterenol, and mice were pretreated with rotigotine or RoMS before inducing myocardial ischemic injury. The effects of rotigotine or RoMS therapy on the degree of myocardial ischemic injury were studied by evaluating troponin I level, creatine kinase-MB (CK-MB) activity, and histopathological changes in cardiomyocytes. The dopamine receptor blocker chlorpromazine was used to further investigate the effects of rotigotine or RoMS on myocardial ischemic injury. Furthermore, serum rotigotine concentrations were also assayed. When myocardial ischemia occurred during rotigotine or RoMS administration, troponin I level and CK-MB activity were decreased, and ischemia-induced histopathological changes in cardiomyocytes were alleviated. The effects of rotigotine were maintained only 12 h and after that no protective effect was observed. RoMS releases continuously into the circulation after intramuscular injection. The cardioprotective effects of RoMS were maintained 14 days after a single RoMS administration. When combined with chlorpromazine, the protective effects of rotigotine on myocardial ischemic injury were eliminated, and the protective effects of RoMS were also partially abolished. In the animal model of myocardial ischemia, pretreatment with rotigotine or RoMS does not deteriorate, but can alleviate cardiomyocyte injury. Furthermore, RoMS pretreatment show long-term and continuous protective effects on cardiomyocyte injury. RoMS therapy in PD patients at high risk for cardiovascular diseases may attenuate the degree of cardiomyocyte injury caused by ischemia.

Effects of Rotigotine Extended‐release Microspheres Therapy on Stroke‐induced Brain Injury

ObjectiveRotigotine, a non‐ergot dopamine agonist, is a novel compound for the treatment of Parkinson's disease (PD). Rotigotine extended‐release microspheres (RoMS) was developed by Shandong Luye Pharmaceutical Co., Ltd. Previous studies demonstrate that a single RoMS administration continuously release rotigotine for 2 weeks. The purpose of this study is to investigate the effect of RoMS therapy on stroke‐induced brain injury in mice.MethodsCD‐1 mice were intramuscularly administered with a single RoMS (10 or 40 mg/kg). At 7th or 14th day after RoMS treatment, intracerebral hemorrhage model was established by an intrastriatal injection of bacterial collagenase. After 24 h, Garcia test and brain water content were evaluated. Sprague‐Dawley rats were treated with RoMS (5 or 20 mg/kg) and then they were subjected to 90‐minute cerebral ischemia followed by reperfusion. After 24 h, functional recovery was assessed by cylinder test, beam walking test, and adhesive test. Brain water content assay was also conducted.ResultsOn the 7th and 14th day, the Garcia test score in the control group was 18.00 ± 0.11, 18.00 ± 0.24. The Garcia test score in the model group was decreased (7.00 ± 1.12, 7.75 ± 1.75, respectively, P&lt;0.01). The Garcia test score in RoMS groups were increased (P&lt;0.01). On the 7th and 14th day, the perihematomal brain water content in the ipsilateral basal ganglia of the model group (83.08 ± 1.46%, 82.91 ± 1.28%) was augmented compared with that of the control group (77.22 ± 1.60%, 77.72 ± 0.88%, P&lt;0.01), while the perihematomal brain water content did not show a difference among RoMS groups and the model group. On the 7th and 14th day, the rats in the model group (67.7 ± 0.06%, 68.4 ± 0.06%) displayed a significant preference for the use of the unimpaired forepaw compared with control group (51.9 ± 0.04%,48.2 ± 0.03%, P&lt;0.01). The rats in the model group (10.0 ± 3.4 s, 8.1 ± 1.0 s) spent a markedly longer time crossing the beam compared with control group (3.6 ± 0.5 s, 3.6 ± 0.7 s, P&lt;0.01). The contact time in the model group (59.1 ± 50.5 s, 82.2 ± 43.1 s) were significantly prolonged compared with the sham group (16.4 ± 3.5 s, 12.9 ± 3.3 s, P&lt;0.01). RoMS therapy neither attenuated nor deteriorated the neurological function of ischemic stroke rats. The brain water content of ischemic hemisphere in the model group (79.8 ± 1.38%, 80.6 ± 1.35%) was increased significantly (78.0 ± 0.56%, 78.4 ± 0.22%, P&lt;0.01). RoMS therapy had no effect on the brain water content in ischemic hemisphere.ConclusionIf the animals treated with RoMS are on an attack of stroke, the brain injury will be neither attenuated nor deteriorated. RoMS therapy in PD patients with high risk factor for stroke does not aggravate stroke‐induced brain injury, which provides supports for clinical application of RoMS.Support or Funding InformationNational Natural Science Foundation of China (Grant No. 81573639).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Tobacco smoking and psychotropic drugs

Rotigotine is a dopamine receptor agonist that can improve motor function in Parkinson's disease (PD) patients. Rotigotine extended-release microsphere (RoMS) is an extended-release intramuscular formulation that exhibits a sustained release of rotigotine over a 14-day period. The clinical trials of RoMS has been carried out in USA and China. The purpose of this study is to observe the effects of RoMS therapy on myocardial ischemic injury in mice, to know whether RoMS alleviate or deteriorate the myocardial ischemic injury while PD patient has onset of myocardial ischemia concurrent after administered with RoMS. A mouse model of myocardial ischemia was established using isoproterenol, and mice were pretreated with rotigotine or RoMS before inducing myocardial ischemic injury. The effects of rotigotine or RoMS therapy on the degree of myocardial ischemic injury were studied by evaluating troponin I level, creatine kinase-MB (CK-MB) activity, and histopathological changes in cardiomyocytes. The dopamine receptor blocker chlorpromazine was used to further investigate the effects of rotigotine or RoMS on myocardial ischemic injury. Furthermore, serum rotigotine concentrations were also assayed. When myocardial ischemia occurred during rotigotine or RoMS administration, troponin I level and CK-MB activity were decreased, and ischemia-induced histopathological changes in cardiomyocytes were alleviated. The effects of rotigotine were maintained only 12 h and after that no protective effect was observed. RoMS releases continuously into the circulation after intramuscular injection. The cardioprotective effects of RoMS were maintained 14 days after a single RoMS administration. When combined with chlorpromazine, the protective effects of rotigotine on myocardial ischemic injury were eliminated, and the protective effects of RoMS were also partially abolished. In the animal model of myocardial ischemia, pretreatment with rotigotine or RoMS does not deteriorate, but can alleviate cardiomyocyte injury. Furthermore, RoMS pretreatment show long-term and continuous protective effects on cardiomyocyte injury. RoMS therapy in PD patients at high risk for cardiovascular diseases may attenuate the degree of cardiomyocyte injury caused by ischemia.

Correction to: Effectiveness of Rotigotine plus intensive and goal‑based rehabilitation versus Rotigotine alone in “de‑novo” Parkinsonian subjects: a randomized controlled trial with 18‑month follow‑up

The original version of this article unfortunately contained a mistake. The funding information was incorrect. The corrected funding information is given below.

A noninterventional study evaluating the effectiveness of rotigotine and levodopa combination therapy in younger versus older patients with Parkinson’s disease

ABSTRACTBackground: PD0013 was a 6-month noninterventional study in clinical practice comparing effectiveness/tolerability of rotigotine+levodopa in younger (<70 years) vs. older (≥70 years) Parkinson’s disease (PD) patients.Methods: Patients previously received levodopa for ≥6 months as monotherapy/in combination with another dopamine-agonist (DA). Primary variable: Unified PD Rating Scale (UPDRS) Part-II change from baseline to end-of-observation-period (EOP).Results: 91 younger/99 older patients started rotigotine; 68 younger/62 older patients completed the study. Most switched from levodopa+another DA. Addition of rotigotine as first DA was more common in older patients (20.2% vs.15.4%). Mean ± SD rotigotine-exposure: 6.1 ± 3.4 mg/24h younger vs. 4.9 ± 2.4 mg/24h older. Eleven patients changed levodopa dose.At EOP, improvement in mean UPDRS-II was greater in younger patients (p = 0.0289). UPDRS-II responder-rate (≥20% decrease in UPDRS-II score) was higher in younger patients (42.3% vs. 25.9%). Improvement across age groups was similar on PD Sleep Scale-2 and Clinical Global Impressions-Improvement Scale. Adverse drug reactions (ADRs), and discontinuations because of ADRs, were more common among older patients. There were no new safety signals.Conclusions: Despite low rotigotine doses, when added to levodopa/switched from levodopa+another DA, rotigotine led to greater improvement in UPDRS-II in younger patients (<70 years). Individual patient data revealed clinically meaningful improvements in UPDRS-II in both groups.

Rotigotine Improves Abnormal Circadian Rhythm of Blood Pressure in Parkinson’s Disease

Introduction: Cardiovascular autonomic failure is commonly associated with Parkinson’s disease (PD), affecting the daily lives of patients. Rotigotine was recently reported not to influence cardiovascular autonomic responses in contrast to other dopaminergic drugs. The effect of rotigotine on daily blood pressure (BP) fluctuations might reflect autonomic failure in patients with PD. Methods: Twenty-five PD patients who were receiving rotigotine and 12 patients not receiving rotigotine were recruited. Systolic BP during the daytime and nighttime was measured by 24-h BP monitoring at an interval of 2 years. The patients were divided into 3 groups according to the BP fluctuation type: dippers (nocturnal fall in BP ≥10%), non-dippers (0–10%), and risers (< 0%). The time course of BP was compared between the patients given rotigotine and those not given rotigotine. Results: Among the 25 patients who received rotigotine, the BP type worsened in 2 patients, was unchanged in 16 patients, and improved in 7 patients. Among the 12 patients who were not receiving rotigotine, the BP type worsened in 5 patients, was unchanged in 4 patients, and improved only in 3 patients (p = 0.042). Conclusion: Rotigotine improves the abnormal circadian rhythm of BP in patients with PD. Rotigotine was suggested to have favorable effects on cardiovascular autonomic responses and circadian rhythm in patients with PD.

Effectiveness of Rotigotine plus intensive and goal-based rehabilitation versus Rotigotine alone in \u201cde-novo\u201d Parkinsonian subjects: a randomized controlled trial with 18-month follow-up

BackgroundDopamine Replacement Therapy (DRT) represents the most effective treatment for Parkinson’s disease (PD). Nevertheless, several symptoms are unresponsive to treatment and its long-term use leads to serious side effects. To optimize the pharmacological management of PD, dopamine-agonists are often prescribed to “de-novo” patients. Moreover, several studies have shown the effectiveness and the synergic effect of rehabilitation in treating PD.ObjectiveTo evaluate the synergism between DRT and rehabilitation in treating PD, by investigating the short and the long-term effectiveness of a multidisciplinary, intensive and goal-based rehabilitation treatment (MIRT) in a group of patients treated with Rotigotine.Materials and methodsIn this multicenter, single blinded, parallel-group, 1:1 allocation ratio, randomized, non-inferiority trial, 36 “de-novo” PD patients were evaluated along 18 months: 17 were treated with Rotigotine plus MIRT; 19 were treated with Rotigotine alone (R). The primary outcome measure was the total score of Unified Parkinson’s Disease Rating Scale (UPDRS). The secondary outcomes included the UPDRS sub-sections II and III (UPDRS II-III), the 6-Minute Walk Test (6MWT), the Timed Up and Go Test (TUG) and the amount of Rotigotine. Patients were evaluated at baseline (T0), 6 months (T1), 1 year (T2), and at 18 months (T3).ResultsNo differences in UPDRS scores in the two groups (total score, III part and II part, p = 0.48, p = 0.90 and p = 0.40, respectively) were found in the time course. Conversely, a greater improvement in Rotigotine + MIRT group was observed for 6MWT (p < 0.0001) and TUG (p = 0.03). Along time, the dosage of Rotigotine was higher in patients who did not undergo MIRT, at all observation times following T0.ConclusionsOver the course of 18 months, the effectiveness of the combined treatment (Rotigotine + MIRT) on the patients’ global clinical status, evaluated with total UPDRS, was not inferior to that of the pharmacological treatment with Rotigotine alone. Importantly, rehabilitation allowed patients to gain better motor performances with lower DRT dosage.

Effects of rotigotine on clinical symptoms, quality of life and sleep hygiene adequacy in hemodialysis-associated restless legs syndrome

BackgroundRestless legs syndrome (RLS) is a neurological disorder characterized by bothersome symptoms associated with impaired quality of life and sleep hygiene. Rotigotine is a novel therapeutic alternative, although few studies have been published in patients on hemodialysis (HD) with RLS treated with rotigotine. Objectives(1) To establish the prevalence of RLS in our HD unit. (2) To evaluate the efficacy and safety profile of rotigotine and its effect on symptoms, quality of life and sleep hygiene in our HD population with RLS. Material and methodsA single-center, 12-week prospective study. Two stages (6 weeks): stage 1 (no treatment) and stage 2 (rotigotine). We analyzed: (1) Demographic data, biochemistry data, HD suitability parameters and RLS medical treatment data. (2) Lower extremity symptoms questionnaire (QS). (3) RLS severity symptoms scale (SRLSS). (4) RLS quality of life: John Hopkins RLS-QoL (JH-QoL). (5) Sleep hygiene: SCOPA Scale. ResultsWe included 66 HD patients, 14 with RLS; 44.4% male, 70.2±9.9 years and 111.1±160.8 months on HD and 22.9% RLS. Exclusively in stage 2, a significant improvement for QS (10±2.4 vs. 5.7±1.0), SRLSS (21±4 vs. 5.7±4.6), JH-QoL (22.1±4.4 vs. 4.3±4.0) and SCOPA (16±5.3 vs. 6.7±1.9) were observed. A 77.7 and 11.1%, showed partial (>20%) and complete (>80%) remission, respectively, while 55.5% achieved “zero” symptoms. Only one patient had gastrointestinal intolerance and none experienced augmentation effect. No changes in biochemical data, suitability for dialysis or medical treatment were found. The inter-group analysis showed a significant improvement in relation to QS, SRLSS, JH-QoL and SCOPA in stage 2. ConclusionsRLS showed a considerable prevalence in our HD unit. Rotigotine improved clinical symptoms, quality of life and sleep hygiene in RLS patients on HD and was found to be a safe drug with minimal side effects and total therapeutic compliance. Nevertheless, future studies should be performed to confirm the benefits of rotigotine in RLS patients on hemodialysis.

Rotigotine, a dopamine receptor agonist, increased BDNF protein levels in the rat cortex and hippocampus.

Brain-derived neurotrophic factor (BDNF) critically controls the fate and function of the neuronal network and has received much attention as a target of many brain diseases. Dopaminergic system dysfunction has also been implicated in a variety of neuropsychiatric diseases. Rotigotine, a non-ergot dopamine receptor agonist, is used in the treatment of Parkinson's disease and restless legs syndrome. To investigate the effects of rotigotine on neuronal functions both in vivo and in vitro, rats and primary cortical neurons were administered rotigotine, and the mRNA and protein expression levels of BDNF, its receptor TrkB and downstream signaling molecules, and synaptic proteins were determined. We found that BDNF protein was increased in the cortex and hippocampus of rats after 7days of rotigotine treatment. In contrast, BDNF mRNAs were reduced 6h after rotigotine treatment in cultured neurons presumably through the transient suppression of neuronal activity. We identified differential expression of D1, D2, and D3 receptors in the rat brain and cultured neurons. The observed increase in the expression of BDNF protein in the cortex and hippocampus after subchronic administration of rotigotine suggests that it may exert its medical effect in part through improving BDNF function in the brain. In addition, our results highlight the complex relationships between rotigotine and BDNF expression, which depend on the brain region, time course, and dose of the drug.

Effect of rotigotine on 25 patients with Parkinson's disease for 156 weeks, a single-arm, prospective study

Effect of rotigotine on 25 patients with Parkinson's disease for 156 weeks, a single-arm, prospective study