Neurobiology of l-DOPA induced dyskinesia and the novel therapeutic strategies

Parkinson's disease (PD) is a neurological disorder characterized by tremors, rigidity and bradykinesia. PD is caused by selective degeneration of the dopaminergic neurons, which originate in the substantia nigra pars compacta (SNc) and project into the striatum. Levodopa is the most effective drug, used in the treatment of PD. However, the long-term use of levodopa produce complications which are highly disabling fluctuations and dyskinesias and representing one of the major challenge to the existing drug therapy of PD. Recent studies has indicated that the pulsatile stimulation of striatal postsynaptic receptors led to sensitization of dopaminergic receptors which leads to levodopa induced dyskinesias. In spite of the extensive research in this field, the pathogenesis of levodopa induced dyskinesia is still unclear. In recent years animal models of PD has provided important information to understand the effect of specific receptors and post-receptor molecular mechanisms underlying the development of dyskinetic movements. The present review is aimed to discuss the neurobiological mechanisms of levodopa induced dyskinesia and the therapeutic strategies to overcome this problem. (C) 2015 Elsevier Masson SAS. All rights reserved.