Tozadenant (SYN115) is an adenosine A2A receptor antagonist(Ki of 11.5 nM and 6 nM on human and rhesus,respectively)

When compared to the drugs tested alone, Radiprodil and Tozadenant combination led to a significant increase of motor activity and an improvement of motor disability in MPTP-treated marmosets. In addition, the motor restoration brought about by the combination was almost completely devoid of dyskinesia[1]

Before initiating the Radiprodil & Tozadenant combination experiment, 14 primates were challenged with a dose of 8 mg/kg (po) of L-Dopa and behaviour was recorded for 5 hours. This "Pre-L-Dopa-test" was used to select the 12 subjects required for the study. Their response to the L-Dopa challenge was subsequently used as a comparator to the ensuing response to the different drug treatments and combinations. The effects of the drugs alone or in combination were assessed after acute oral gavage.This experiment investigated the effects on motor deficits of Radiprodil plus Tozadenant twice daily at an interval of 5 hrs according to a modified Latin square design in n = 12 MPTP-treated marmosets. At the time of the second drugs administration a novel object (cotton reel, table tennis ball) was placed into the cage. The four different treatments were (1) Tozadenant (150 mg/kg) plus Radiprodil (2.0 mg/kg), (2) Tozadenant (150 mg/kg) plus vehicle, (3) Radiprodil (2.0 mg/kg) plus vehicle, (4) vehicle[1].