Dopamine agonists such as pramipexole (PPX) have first been proposed as adjunctive treatment to levodopa (L-DOPA) for patients with Parkinson’s disease (PD) and then as a monotherapy alternative to alleviate dyskinesia. Treatment with PPX has overall been associated with improvement in parkinsonian symptoms. Although the majority of placebo-controlled studies demonstrated that dyskinesia was more prevalent in the PPX compared to the placebo groups, some studies did not detect any dyskinesia as a side effect of this medication. PPX was consistently associated with lower risk for developing dyskinesia compared to L-DOPA. Moreover, the presence of these symptoms in the placebo groups suggests involvement of non-PPX-related factors for developing dyskinesia. It is suggested that future research should aim at ascertaining whether cotherapy with L-DOPA, PPX dosage, and other patient characteristics are contributory factors for the development of PPX-related dyskinesia in patients with PD. 1. Dyskinesia in Parkinson’s Disease Parkinson’s disease (PD) is a neurodegenerative disease characterised by motor (particularly tremor, rigidity, and bradykinesia) as well as cognitive and behavioural symptoms. The pathophysiology of PD has been related to the degeneration of nigrostriatal dopaminergic pathways [1], and this has allowed the treatment for PD to be targeted towards modulating dopamine (DA) neurotransmission (Figure 1). Figure 1: Treatment of Parkinson’s disease: anti-Parkinson’s medications modulate key stages of dopaminergic neurotransmission. Abbreviations: TYR: tyrosine, L-DOPA: L-3, 4-dihydroxyphenylalanine, DA: dopamine, MAO: monoamine oxidase, DAT: DA reuptake transporter, COMT: catechol-O-methyltransferase, 3-MT: 3-methoxytyramine, DAR: DA receptor. Anti-Parkinson’s drugs are highlighted in bold. Pointed arrows indicate stimulatory, and closed arrows indicate inhibitory activity. Levodopa (L-DOPA) has long been the mainstay of PD treatment although over time patients on L-DOPA develop motor complications including dyskinesias, which are associated with the timing of drug administration. Dyskinesias are involuntary muscular contractions and include choreic, dystonic, myoclonic, and tic movements [2]. After 5 and 10 years of L-DOPA therapy, 91% and all of the participants in a longitudinal cohort ( ), respectively, experienced dyskinesias [3]. Another study also identified that cumulative L-DOPA dosage was significantly associated with the development of dyskinesia [4]. Given that dyskinesias has been consistently shown to negatively affect patients’
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