ADJUNCTS TO DOPAMINE REPLACEMENT - A PRAGMATIC APPROACH TO REDUCING THE PROBLEM OF DYSKINESIA IN PARKINSONS-DISEASE

Dyskinesias following long-term dopamine replacement therapy ate a maj or limitation of current treatments for Parkinson's disease. Recently, attention has been focused on the concept of using non-dopaminergic a djuncts to currently available therapies in an attempt to reduce the p roblem of dyskinesia. Thus, an enhanced understanding of the neural me chanisms underlying dyskinetic symptoms has led to the realization tha t it might be possible to manipulate non-dopaminergic systems and redu ce dyskinesia without compromising the anti-parkinsonian efficacy of d rugs such as L-dopa. This article discusses how non-dopaminergic manip ulations could reverse the abnormalities in basal ganglia circuitry re sponsible for generating dyskinesia. It is proposed that potential ant i-dyskinetic drugs might include glutamate (NMDA) receptor antagonists , opioid receptor antagonists, cannabinoid receptor agonists or antago nists, or, adrenergic receptor antagonists, and 5-HT-enhancing agents.