Vipadenant

A potent and selective A2A adenosine receptor with Ki of 1.3 nM; displays 50-fold selectivity over A1 and A2B, and no activity against A3, P450 isoforms and hERG; shows excellent preclinical pharmacokinetics, and demonstrates strong oral activity in commonly used models of Parkinson's disease. (In Vivo) :Vipadenant (0.3-30 mg/kg) produces a dose-dependent reduction in catalepsy. Vipadenant (10 mg/kg) does not produce any statistically significant dyskinetic episodes in 6-OHDA-lesioned rats during a 19-day dosing regimen. In the mouse and rat haloperidol-induced hypolocomotion models, vipadenant has a minimum effective dose of 0.1 and 1 mg/kg, respectively. Vipadenant (3 and 10 mg/kg, p.o.) is able to increase contralateral rotations in 6-OHDA lesioned rats.