Neurodegenerative Disease Parkinson’s Disease
Monoamine Oxidase Type B Inhibitors in the Treatment of Early Parkinson’s Disease
Cherian Abraham Karunapuzha, MD,1 Shilpa Chitnis, MD, PhD2 and Richard B Dewey, Jr, MD3 1. Movement Disorders Fellow; 2. Assistant Professor of Neurology; 3. Professor of Neurology, University of Texas Southwestern Medical Center
Abstract
Therapy in Parkinson’s disease (PD) needs to be individualized since patients differ in symptom expression and responsiveness to pharmacotherapy. Disease-modifying drugs should be considered early in the course of the disease, but none is currently US Food and Drug Administration (FDA)-approved for this indication. Symptomatic therapies should be optimized to keep the patient independent and functioning for as long as possible. Early therapies in PD consist of dopamine agonists, monoamine oxidase type B (MAO-B) inhibitors, and, in some patients, carbidopa–levodopa (depending on age and symptom severity). MAO-B inhibitors are approved by the FDA for monotherapy in treatment of early PD and as an adjunct to levodopa in advanced disease. This article focuses on the role of MAO-B enzymes in PD pathogenesis and reviews clinical evidence for the use of MAO-B inhibitors in the treatment of early PD.
Keywords
Parkinson’s disease, monoamine oxidase type B (MAO-B) inhibitors, rasagiline, selegiline, Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, Rasagiline Mesylate (TVP-1012) in Early Monotherapy for PD Outpatients (TEMPO) study, Effect of Rasagiline Mesylate in Early PD patients (ADAGIO) study, dopamine agonists, carbidopa–levodopa
Disclosure: Cherian Abraham Karunapuzha, MD, has no conflicts of interest to declare. Shilpa Chitnis, MD, PhD, is a consultant for Medtronic and on the speaker’s bureau for Medtronic, Teva Neuroscience, Ipsen, and Lundbeck. Richard B Dewey, Jr, MD, is on the speaker’s bureau for Teva Neuroscience, GlaxoSmithKline, and Ipsen, is a consultant for Teva Neuroscience, and receives grant support from the National Institutes of Health (NIH). Received: May 28, 2010 Accepted: July 19, 2010 Citation: US Neurology, 2010;6(1):36–40 Correspondence: Richard B Dewey, Jr, MD, UT Southwestern Medical Center, 5323 Harry Hines Blvd, J3134 E, Dallas, TX 75390-9036. E:
richard.dewey@
utsouthwestern.edu
Support: The publication of this article was funded by Teva Neuroscience. The views and opinions expressed are those of the authors and not necessarily those of Teva Neuroscience.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder. It has been classically described as a movement disorder involving the striato-nigral pathway characterized by resting tremor, bradykinesia, rigidity, and postural instability. It is now considered a multisystem disorder that includes motor and non-motor symptoms.1
The early
form of the disease can have predominantly non-motor symptoms, which are non-specific and can be overlooked for years until the cardinal motor symptoms emerge. The non-motor symptoms can be sensory, cognitive/psychiatric, or autonomic. The non-motor features by themselves can be a considerable cause of disability for many patients.
Options for Initiation of Treatment in Parkinson’s Disease
There are several US Food and Drug Administration (FDA)-approved options for monotherapy in PD. Treatment of early disease can be initiated with amantadine, anticholinergic agents, monoamine oxidase type B (MAO-B) inhibitors, dopamine agonists or carbidopa–levodopa (CD/LD). Levodopa initially provides stable relief for the symptoms of PD; however, 50–90% of patients develop motor complications (such as motor fluctuations and dyskinesias) after five to 10 years of CD/LD
36
therapy.2,3
Delaying the initiation of levodopa may be appropriate to defer these problems. Dopamine agonists are useful in initial monotherapy for controlling motor symptoms with less risk of developing motor complications. Studies suggest that the mechanism by which agonists delay complications is by permitting a delay in the starting of levodopa rather than by any direct disease-modifying effect.4
Dopamine agonists
are associated with a number of side effects such as hallucinations, impulse-control disorders, excessive daytime sleepiness, vomiting, and orthostatic hypotension.5,6
helpful with rigidity and akinesia initially,7
Amantadine has been shown to be somewhat but these effects are not long-
lasting and livedo reticularis, edema, confusion, and hallucinations are common side effects. Anticholinergics can be used in younger patients with predominant tremor,8
but their use is limited by peripheral
cholinergic side effects, confusion, memory impairment, and possible withdrawal effects.
Monoamine Oxidase Type B Inhibition and Parkinson’s Disease
Dopaminergic neurons decline steadily in PD, with motor symptoms emerging when about 50% of nigral neurons have degenerated.9
At © TOUCH BRIEFINGS 2010
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