The past changes and future perspectives on Parkinson's disease therapeutics in Japan

The treatment of Parkinson's disease was exclusively restricted to levodopa until the mid-1980s, and levodopa stays the gold standard in 2016. Improvement in understanding for the functional organization of basal ganglia paved the way for deep brain stimulation that provides dramatic benefit against levodopa-induced motor complications. Novel dopamine agonists, catecholmethyltransferase inhibitors, and monoamine oxidase B inhibitors offered more continuous dopamine delivery that can attenuate motor complications. The early dopamine agonists' usage can postpone the onset of dyskinesia. The focus of the randomized controlled trials has recently been expanded to nonmotor symptoms, such as depression, dementia, and psychosis. Despite these therapeutic progresses and challenges, substantial inhibition of disease progression remains yet to be realized. For future therapeutic interventions, it is required to develop newer molecular targets, new disease models, novel clinical study designs, and sensitive biomdarkers to detect patients at the early stage and assess the efficacy of disease modification.