FACING DYSKINESIA IN PARKINSON'S DISEASE: NONDOPAMINERGIC APPROACHES

L-DOPA has been the gold standard for the treatment of Parkinson's disease for the last 5 decades. Nevertheless, problems with long-term use, such as motor fluctuations and dyskinesias, have led investigators to search for alternative therapies and for various approaches designed to minimize or ameliorate dyskinesias. Dopaminergic strategies are being studied, including continuous drug infusion. Moreover, nondopaminergic approaches such as serotonergic agents, adenosine A(2A) receptor antagonists and amantadine are also being investigated. Serotonin 5-HT2A receptor antagonists and 5-HT1A receptor agonists have been studied for their antidyskinetic effects. Adenosine A(2A) receptor antagonists exert antiparkinsonian effects in animal models and several candidates have progressed to phase II or Ill clinical testing. Generally, these agents have been shown to decrease L-DOPA "off" time and increase "on" time, without worsening L-DOPA-induced dyskinesias. Of all the drugs tested so far, amantadine appears to produce the most consistent antidyskinetic actions. In conclusion, numerous approaches appear to offer promise for the management of dyskinesias, one of the most troubling aspects of the current treatment of Parkinson's disease.