Istradefylline (DB11757): A Comprehensive Monograph on a First-in-Class Adenosine A2A Receptor Antagonist for Parkinson's Disease

Section 1: Executive Summary

Istradefylline, marketed under the brand names Nourianz® and Nouriast®, is a first-in-class, selective adenosine A2A receptor antagonist.[1] It represents a novel, non-dopaminergic therapeutic strategy for the management of Parkinson's Disease (PD). The medication is indicated as an adjunctive treatment to levodopa/carbidopa for adult patients with PD who experience "off" episodes—debilitating periods of recurrent motor and non-motor symptoms that occur as the effects of levodopa diminish.[3]

The mechanism of action of istradefylline is distinct from all other classes of anti-Parkinsonian drugs. It selectively targets and blocks overactive adenosine A2A receptors, which are densely expressed in the basal ganglia. This action primarily modulates the indirect striatopallidal ("no-go") pathway, reducing excessive inhibitory GABAergic output and helping to restore a more functional balance within the brain's motor control circuitry.[5]

The clinical efficacy of istradefylline has been established through an extensive development program. Pivotal trials have demonstrated a modest but statistically significant reduction in daily "off" time and a corresponding increase in "on" time without troublesome dyskinesia when compared to placebo.[8] However, the overall clinical data package is characterized by a notable heterogeneity in outcomes across multiple large-scale studies, a factor that has profoundly influenced its global regulatory reception.[10]