Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia—Literature Review

Abstract

Levodopa remains the primary drug for controlling motor symptoms in Parkinson’s disease through the whole course, but over time, complications develop in the form of dyskinesias, which gradually become more frequent and severe. These abnormal, involuntary, hyperkinetic movements are mainly characteristic of the ON phase and are triggered by excess exogenous levodopa. They may also occur during the OFF phase, or in both phases. Over the past 10 years, the issue of levodopa-induced dyskinesia has been the subject of research into both the substrate of this pathology and potential remedial strategies. The purpose of the present study was to review the results of recent research on the background and treatment of dyskinesia. To this end, databases were reviewed using a search strategy that included both relevant keywords related to the topic and appropriate filters to limit results to English language literature published since 2010. Based on the selected papers, the current state of knowledge on the morphological, functional, genetic and clinical features of levodopa-induced dyskinesia, as well as pharmacological, genetic treatment and other therapies such as deep brain stimulation, are described.

Botulinum Toxin Therapy for Oromandibular Dystonia and Other Movement Disorders in the Stomatognathic System

“…In severe cases, repeated dyskinetic movements of the lower lip can result in the penetration of the skin [82]. Levodopa remains the primary medicine for controlling motor symptoms in Parkinson's disease; however, complications cause dyskinesia [98][99][100]102]. Hyperkinetic movements are triggered by the ON phase and occur during the OFF phase or in both phases [102].…”

Molecular Mechanisms and Therapeutic Strategies for Levodopa-Induced Dyskinesia in Parkinson’s Disease: A Perspective Through Preclinical and Clinical Evidence

“…Prolonged release of ropinirole has the potency to delay dyskinesia more than the increased dose of L-DOPA in patients. Rotigotine, a D1 receptor agonist, can also be used as a replacement for L-DOPA to prevent dyskinesia, but more investigation is required ( Hutny et al, 2021 ).…”

“…This drug increases the bioavailability of L-DOPA, which has been proved in many experimental studies. Dyskinesia, insomnia, and dizziness are the disadvantages of opicapone ( Hutny et al, 2021 ).…”

“…In treatment therapy of diphasic dyskinesia, the addition of DA agonists or drugs that prolong L-DOPA, that is, COMT inhibitors or monoamine oxidase B inhibitors, are administered. D3 receptor antagonist IRL790 can also be given to a patient for maintaining psychomotor stability ( Schaeffer et al, 2014 ; Hutny et al, 2021 ).…”

“…Thus, the results obtained by using the L-DOPA and nalbuphine combination therapy might be an outcome of the therapy’s dualistic nature. However, µ receptor agonism monotherapy was able to downgrade the incidence of LID in the MPTP parkinsonian rat model ( Hutny et al, 2021 ).…”