Clinical pharmacology and efficacy of rotigotine (Neupro® patch) in the treatment of restless leg syndrome

Ferini‐Strambi, Luigi; Marelli, Sara; Galbiati, Andrea

doi:10.1080/17425255.2016.1194393

Cited by 14 publications

(2 citation statements)

References 53 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both D3 and D1 receptors are expressed in the lumbar spinal cord (Zhu et al, 2007 ), and DA can up- or downregulate cellular and network functions in a dose-dependent manner (Missale et al, 1998 ; Thirumalai and Cline, 2008 ; Clemens et al, 2012 ). Current DA-based RLS treatment options center around D3 receptor agonists (Ferini-Strambi et al, 2016 ; Ferré et al, 2017 ), but their effect is reduced over time and can cause a worsening of the symptoms (augmentation) (Allen et al, 2011 ; García-Borreguero and Williams, 2011 ; Earley et al, 2017 ; Trenkwalder et al, 2017 ). While we have previously shown that D3 receptor agonists and antagonists can oppositely regulate spinal reflex amplitudes (SRAs) of WT in vitro while they do not alter SRAs in D3KO (Clemens and Hochman, 2004 ), we here wanted to test how these neuromodulators act in vivo , and how their effects compare with the Meis1KO animals (Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome

Meneely

Dinkins

Kassai

et al. 2018

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Restless Legs Syndrome (RLS) is often and successfully treated with dopamine receptor agonists that target the inhibitory D3 receptor subtype, however there is no clinical evidence of a D3 receptor dysfunction in RLS patients. In contrast, genome-wide association studies in RLS patients have established that a mutation of the MEIS1 gene is associated with an increased risk in developing RLS, but the effect of MEIS1 dysfunction on sensorimotor function remain unknown. Mouse models for a dysfunctional D3 receptor (D3KO) and Meis1 (Meis1KO) were developed independently, and each animal expresses some features associated with RLS in the clinic, but they have not been compared in their responsiveness to treatment options used in the clinic. We here confirm that D3KO and Meis1KO animals show increased locomotor activities, but that only D3KO show an increased sensory excitability to thermal stimuli. Next we compared the effects of dopaminergics and opioids in both animal models, and we assessed D1 and D3 dopamine receptor expression in the spinal cord, the gateway for sensorimotor processing. We found that Meis1KO share most of the tested behavioral properties with their wild type (WT) controls, including the modulation of the thermal pain withdrawal reflex by morphine, L-DOPA and D3 receptor (D3R) agonists and antagonists. However, Meis1KO and D3KO were behaviorally more similar to each other than to WT when tested with D1 receptor (D1R) agonists and antagonists. Subsequent Western blot analyses of D1R and D3R protein expression in the spinal cord revealed a significant increase in D1R but not D3R expression in Meis1KO and D3KO over WT controls. As the D3R is mostly present in the dorsal spinal cord where it has been shown to modulate sensory pathways, while activation of the D1Rs can activate motoneurons in the ventral spinal cord, we speculate that D3KO and Meis1KO represent two complementary animal models for RLS, in which the mechanisms of sensory (D3R-mediated) and motor (D1R-mediated) dysfunctions can be differentially explored.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome

Meneely

Dinkins

Kassai

et al. 2018

Front. Behav. Neurosci.

View full text Add to dashboard Cite

show abstract

“…However, few studies have aimed to characterize the underlying mechanisms of RLS in PD cohorts specifically. Generally, brain imaging studies evaluating dopaminergic function in iRLS patients have yielded inconclusive results though some have provided evidence for the pathogenic role of the dopaminergic dysfunction, which is in line with the effectiveness of dopaminergic therapies ( 119 ).…”

Section: Restless Leg Syndromementioning

confidence: 94%

Neuroimaging of Sleep Disturbances in Movement Disorders

et al. 2018

View full text Add to dashboard Cite

Sleep dysfunction is recognized as a distinct clinical manifestation in movement disorders, often reported early on in the disease course. Excessive daytime sleepiness, rapid eye movement sleep behavior disorder and restless leg syndrome, amidst several others, are common sleep disturbances that often result in significant morbidity. In this article, we review the spectrum of sleep abnormalities across atypical Parkinsonian disorders including multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), as well as Parkinson's disease (PD) and Huntington's disease (HD). We also explore the current concepts on the neurobiological underpinnings of sleep disorders, including the role of dopaminergic and non-dopaminergic pathways, by evaluating the molecular, structural and functional neuroimaging evidence based on several novel techniques including magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Based on the current state of research, we suggest that neuroimaging is an invaluable tool for assessing structural and functional correlates of sleep disturbances, harboring the ability to shed light on the sleep problems attached to the limited treatment options available today. As our understanding of the pathophysiology of sleep and wake disruption heightens, novel therapeutic approaches are certain to transpire.

show abstract

D3 receptor agonist efficacy in restless legs syndrome

Galbiati

Ferini‐Strambi

2019

Pharmacology of Restless Legs Syndrome (RLS)

View full text Add to dashboard Cite

Clinical pharmacology and efficacy of rotigotine (Neupro® patch) in the treatment of restless leg syndrome

Cited by 14 publications

References 53 publications

Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome

Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome

Neuroimaging of Sleep Disturbances in Movement Disorders

D3 receptor agonist efficacy in restless legs syndrome

Contact Info

Product

Resources

About