The role of istradefylline in the Parkinson's disease armamentarium.

INTRODUCTION

Adenosine antagonism, i.e. of the A receptor, improves dopamine-sensitive motor behavior in patients with Parkinson's disease with oral levodopa-associated motor complications. Only the xanthine derivative istradefylline is currently approved in Japan and in the US. This compound easily crosses the blood-brain barrier and shows high affinity to A receptors.

AREAS COVERED

This narrative review discusses the place of istradefylline in the current available drug portfolio for Parkinson's disease following a literature research in PubMed.

EXPERT OPINION

Istradefylline is safe and well tolerated. Its efficacy was pronounced, when patients were on a lower chronic oral levodopa regimen. Levodopa causes a homocysteine elevation, which reflects an impaired methylation potential. As a result, an upregulation of A receptor occurs and weakens the efficacy of istradefylline as modulator of dopamine effects on motor behavior in Parkinson's disease. This is the hypothetical reason why clinical trials failed, when patients were on a higher chronic levodopa regimen.A way out of this dilemma is to enable higher dosing of istradefylline and substitution of L-dopa with compounds, which do not influence the methylation capacity. Long-term trials may show these levodopa sparing and thus motor complications delaying effects of istradefylline.