Motor complications, levodopa metabolism and progression of Parkinson's disease

Introduction: Oxidative stress is an essential component of neuronal death in Parkinson's disease (PD). Clinically, progression of PD is also characterised by onset of motor complications (MC). MC results from the peripheral and central degree of fluctuations of levodopa (LD) and of dopamine. Areas covered: This review highlights aspects of LD and dopamine metabolism in chronic neurodegeneration in PD. A Medline search (terms: homocysteine, LD, PD, progression [from 2000 onwards]) was performed and considered preclinical and clinical investigations. The author discusses pharmacokinetic and metabolic aspects of chronic LD administration in PD patients and provides a therapeutic concept to reduce probable PD accelerating consequences of chronic LD application. Expert opinion: The author suggests that the future 'ideal' oral LD therapy should be homocysteine-reducing, methyl-group-donating, oxidative-stress-decreasing and antiglutamatergic while also allowing continuous delivery to the brain. This may slow the progression of PD and delay the onset of MC, both of which represent unmet needs in the treatment of PD patients.