An open-label, positron emission tomography study to assess adenosine A2A brain receptor occupancy of vipadenant (BIIB014) at steady-state levels in healthy male volunteers

Clin Neuropharmacol. Mar-Apr 2010;33(2):55-60. doi: 10.1097/WNF.0b013e3181d137d2.


Objective: Adenosine A2A receptor antagonists are potential new treatments for Parkinson disease. We used positron emission tomography (PET) of the A2A receptor radiotracer, [C]SCH442416, to assess binding of the novel A2A antagonist, vipadenant (previously known as BIIB014), to human brain A2A receptors and to investigate the relationship among dose, steady-state plasma levels, and receptor occupancy.

Methods: We used PET to compare [C]SCH442416 uptake before and after blockade with daily oral vipadenant (2.5-100 mg/d for 10 or 11 days) in healthy volunteers (n = 15). We estimated receptor occupancy in brain regions of interest, particularly the putamen, by kinetic modeling of PET data. We estimated the dose, minimal plasma concentration at steady state (Cmin), and area under the plasma concentration curve (AUC0-tau) at the steady state required for saturation (> or =90% receptor occupancy) using Bayesian Emax and logistic regression models.

Results: The estimated receptor occupancy of vipadenant in the brain regions of interest varied from 74% to 94% at the lowest daily dose (2.5 mg) and reached saturation in all regions at 100 mg. In the putamen, the estimated minimal daily dose, steady-state Cmin, and steady-state AUC0-tau required for receptor saturation were 10.2 mg (interquartile range, 28%), 0.097 microg/mL (27%), and 6 microg h/mL (21%), respectively.

Conclusions: This study provides the first evidence that vipadenant occupies A2A receptors in the human brain. Receptor occupancy was related to both dose and plasma levels of vipadenant. These results, coupled with previous efficacy results in animals, justify continued development of vipadenant as a potential treatment for Parkinson disease.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A2 Receptor Antagonists*
  • Adult
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Carbon Radioisotopes / analysis
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Middle Aged
  • Models, Statistical
  • Positron-Emission Tomography / methods*
  • Pyrazoles / analysis
  • Pyrimidines / analysis
  • Pyrimidines / pharmacokinetics*
  • Radioligand Assay / methods
  • Triazoles / pharmacokinetics*


  • 3-(4-amino-3-methylbenzyl)-7-(2-furyl)-3H-(1,2,3)triazolo(4,5-d)pyrimidine-5-amine
  • Adenosine A2 Receptor Antagonists
  • Carbon Radioisotopes
  • Pyrazoles
  • Pyrimidines
  • Triazoles
  • SCH 442416