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Drug profiles

The efficacy of oral adenosine A2A antagonist istradefylline for the treatment of moderate to severe Parkinson’s disease

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Abstract

The moderate and severe stages of Parkinson’s disease (PD) are marked by motor and non-motor complications that still remain difficult to control with the currently available therapy. Adenosine A2A receptor antagonists target non-dopaminergic systems, and have emerged as promising add-on therapy in the management of PD, a little more than a decade ago. While the development of this new drug class was slower than initially expected, istradefylline was recently registered in Japan, because it provides reduction of the off-time, when given in association with levodopa. Effects on some non-motor features have also been suggested, and preliminary studies further suggest a potential neuroprotective effect. Associations of A2A receptor antagonists with dopaminergic agents, as well as enzyme blockers like catechol-O-methyltransferase (COMT) and monoamine oxidase-B (MAO-B) inhibitors, should provide even greater benefit in advanced PD patients, and, thus, a more individualized treatment approach would be at hand.

Key issues
  • There is an ongoing need for new or improved therapeutic approaches for Parkinson’s disease (PD) – a multisystem disorder.

  • Adenosine A2A receptor antagonists have emerged as a potentially efficient add-on therapy to levodopa in patients with moderate to severe PD.

  • The characteristics of istradefylline support its use in patients with PD, particularly for reduction of off-time.

  • Evidence indicates an improvement of motor fluctuations with istradefylline therapy, but new data will be required for registration of the product in Europe and North America.

  • There are other potential benefits of this new drug, such as the neuroprotective effect and the improvement of some non-motor symptoms, including cognition.

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