AbstractBackgroundMB‐204 is a novel Adenosine A2a antagonist that immediately reduces depression and anxiety in animal modelsMethodMB‐204 was dosed one hour prior to its assessment for depression using the forced swim test (FST) and the elevated plus maze (EPM) for anxiety. General locomotive activity was measured as was the effect on rotarod balance as a surrogate for behavioural scores. Receptor occupancy studies were measured using radio‐labelled ligand and ex vivo brain tissue analysis.ResultMB‐204 dose dependently reduced depressive symptoms in the FST (>85%, p<0.001) with no effect on non‐specific locomotive activity or rotarod balance. MB‐204 was found to time and dose dependently occupy the A2a receptor in vivo (p<0.01) which mimicked blood PK levels. In head‐to‐head studies, MB‐204 outperformed Istradefylline (the only approved A2a antagonist for the treatment of Parkinson’s disease) in almost all measurements in the EPM model, and appeared to improve social interactions as measured by sub‐vocalization analyses.ConclusionMB‐204 appears to be an excellent pre‐clinical candidate for the treatment of A2a associated conditions