A 38-year-old man with Parkinson's disease has been on levodopa-carbidopa 100/25 mg TDS for 4 years. He now experiences wearing-off, peak-dose dyskinesias, and unpredictable on-off fluctuations. Which addition to his regimen specifically targets the non-dopaminergic adenosine A2A receptor mechanism implicated in basal ganglia output regulation?
- A Istradefylline — adenosine A2A receptor antagonist reducing indirect pathway overactivity ✓
- B Entacapone — COMT inhibitor extending levodopa half-life
- C Safinamide — selective MAO-B inhibitor with anti-glutamatergic properties
- D Pramipexole — D2/D3 dopamine agonist for off-period reduction
Explanation
Istradefylline is an adenosine A2A receptor antagonist; A2A receptors are highly expressed on striatopallidal (indirect pathway) neurons and their activation increases GABA output to the GPe, enhancing indirect pathway overactivity that characterises PD. Blocking A2A receptors reduces this overactivity and decreases off-time without worsening dyskinesias. It is FDA-approved (2019) as adjunct to levodopa in adults with PD experiencing off episodes. Entacapone inhibits COMT peripherally. Safinamide combines MAO-B inhibition with voltage-gated sodium channel and glutamate release inhibition. Pramipexole is a dopamine agonist.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.