Dyskinesia in Parkinson's disease. Pathophysiology and clinical risk factors

Development of dyskinesia is a common phenomenon during the long-term cours e of Parkinson's disease. During the last few years some but not all pathog enetic mechanisms causing dyskinesias in PD have been better understood. Se verity of Parkinson's disease and levodopa dosing are the main clinical ris k factors. Most concepts underline the significance of pulsatile D1-recepto r stimulation for the development of dyskinesias. The interactions between D1- and D2-mediated STR-Gpi pathways and co-localized neuropeptides are imp ortant: but not fully understood. Glutamatergic overactivity might also be a significant pathogenetic factor. According to these pathophysiological concepts, therapeutic strategies focu s mainly on continuous postsynaptic DA-receptor stimulation by long acting DA agonists or highly selective D2 agonists. Another strategy is the use of NMDA antagonists.