Levodopa-Induced Dyskinesia in Parkinson’s Disease: Pathogenesis and Emerging Treatment Strategies

Abstract

The most commonly used treatment for Parkinson’s disease (PD) is levodopa, prescribed in conjunction with carbidopa. Virtually all patients with PD undergo dopamine replacement therapy using levodopa during the course of the disease’s progression. However, despite the fact that levodopa is the “gold standard” in PD treatments and has the ability to significantly alleviate PD symptoms, it comes with side effects in advanced PD. Levodopa replacement therapy remains the current clinical treatment of choice for Parkinson’s patients, but approximately 80% of the treated PD patients develop levodopa-induced dyskinesia (LID) in the advanced stages of the disease. A better understanding of the pathological mechanisms of LID and possible means of improvement would significantly improve the outcome of PD patients, reduce the complexity of medication use, and lower adverse effects, thus, improving the quality of life of patients and prolonging their life cycle. This review assesses the recent advancements in understanding the underlying mechanisms of LID and the therapeutic management options available after the emergence of LID in patients. We summarized the pathogenesis and the new treatments for LID-related PD and concluded that targeting pathways other than the dopaminergic pathway to treat LID has become a new possibility, and, currently, amantadine, drugs targeting 5-hydroxytryptamine receptors, and surgery for PD can target the Parkinson’s symptoms caused by LID.

Поліпшення Результатів Терапії Хвороби Паркінсона За Допомогою Застосування Леводопи Пролонгованої Дії

“…Основним механізмом, що зумовлює виникнення ускладнень під час лікування ХП, є пульсуюча стимуляція рецепторів [17,18]. Тому доречніше розглядати дискінезію як результат методу введення леводопи, а не як ефект самого препарату.…”

“…Зміна ефективності (зменшення діапазону оптимальної концентрації) леводопи у міру прогресування захворювання[17] …”

Cannabidiol Protects Dopaminergic-like Neurons against Paraquat- and Maneb-Induced Cell Death through Safeguarding DJ-1CYS106 and Caspase 3 Independently of Cannabinoid Receptors: Relevance in Parkinson’s Disease

“…15 However, it presents serious side effects. 16 Therefore, the need for new drugs for the treatment of PD has become increasingly urgent. 17 Interestingly, natural compounds offer therapeutic potential for neurodegenerative disorders.…”

“…l -DOPA (levodopa or l -3,4 dihidroxifenilalanina) is the “gold-standard” drug for the symptomatic treatment of PD . However, it presents serious side effects . Therefore, the need for new drugs for the treatment of PD has become increasingly urgent .…”

Dopamine pathway and Parkinson’s risk variants are associated with levodopa-induced dyskinesia

“…6 This phenomenon occurs due to the progressive dopaminergic loss in PD, resulting in impaired presynaptic storage capacity of dopamine, and is exacerbated by elevated doses of levodopa. [6][7][8] Other pathways have also been implicated in LID development, including the glutamatergic, serotonergic and noradrenergic neural circuits. 7,8 Multiple environmental risk factors affecting LID have been identified, including levodopa dosage and duration of the therapy, use of dopamine agonists, PD age at onset (AAO), disease duration and severity, female sex and lower body mass index (BMI).…”