The safety of istradefylline for the treatment of Parkinson’s disease

Abstract

Introduction: Antagonism of the A_2A receptor improves motor behavior in patients with Parkinson’s disease (PD), according to results of clinical studies which confirm findings of previous experimental research. The xanthine derivative, istradefylline, has the longest half-life out of the available A_2A receptor antagonists. Istradefylline easily crosses the blood–brain barrier and shows a high affinity to the human A_2A receptor.

Areas covered: This narrative review aims to discuss the safety and tolerability of istradefylline against the background of the currently available drug portfolio for the treatment of PD patients.

Expert opinion: Istradefylline was safe and well tolerated in clinical trials, which have focused on l-DOPA-treated PD patients. The future of istradefylline as a complementary drug for modulation of the dopaminergic neurotransmission also relies on its potential to act like an l-DOPA plus dopamine agonist sparing future treatment alternative and to reduce the risk of predominant l-DOPA-related onset of motor complications in addition to its direct ameliorating effect on motor symptoms. Dopamine-substituting drugs may dose-dependently produce systemic side effects, particularly onset of hypotension and nausea by peripheral dopamine receptor stimulation. Istradefylline does not interfere with these peripheral receptors and therefore shows a good safety and tolerability profile.

Keywords:

• adenosine
• dopamine substitution
• istradefylline
• l-DOPA
• Parkinson’s disease

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.