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Drugs

, Volume 79, Issue 13, pp 1367–1374 | Cite as

Recent Clinical Advances in Pharmacotherapy for Levodopa-Induced Dyskinesia

  • Thomas MüllerEmail author
  • Jan-Dominique Möhr
Current Opinion

Abstract

Onset of involuntary movement patterns of the face, body and limbs are known as dyskinesia. They mostly appear in association with long-term levodopa (l-dopa) therapy in patients with Parkinson’s disease. Consequences include patient distress, caregiver embarrassment and reduced quality of life. A severe intensity of this motor complication may result in troublesome disability; however, patients typically prefer motor behaviour with slight, non-troublesome dyskinesia to ‘OFF’ states. Pharmacotherapy of dyskinesia is complex. Continuous nigrostriatal postsynaptic dopaminergic receptor stimulation may delay onset of l-dopa-associated dyskinesia, while non-physiological, ‘pulsatile’ receptor stimulation facilitates appearance of dyskinesia. In the past, there have been many clinical trial failures with compounds that were effective in animal models of dyskinesia. Only the N-methyl-d-aspartate antagonist amantadine has shown moderate antidyskinetic effects in small well-designed clinical studies. Amantadine is an old antiviral compound, which moderately improves impaired motor behaviour. Recently, there has been a resurgence of its use due to the US Food and Drug Administration approval of an extended-release (ER) amantadine formulation for treatment of l-dopa-induced dyskinesia. This pharmacokinetic innovation improved dyskinesia and ‘OFF’ states in pivotal trials, with a once-daily oral application in the evening. Amantadine ER provides higher and more continuous amantadine plasma bioavailability than conventional immediate-release formulations, which require administration up to three times daily.

Notes

Compliance with Ethical Standards

Funding

No funding was received in relation to this article.

Conflict of interest

TM. and J.-D.M. have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the article. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of NeurologySt. Joseph Hospital Berlin-WeißenseeBerlinGermany

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