in mice: Treatment of mice with L-buthionine-(S,R)-sulfoximine (300 mg/kg), an inducer of oxidative stress, caused anxiety-like behavioral effects in elevated plusmaze, open-field, and hole-board tests through the NADPH oxidase pathway; these effects were antagonized by Bay 60-7550 (3 mg/kg) and apocynin (3 mg/kg), an inhibitor of NADPH oxidase. The Bay 60-7550-mediated decrease in oxidative stress and expression of NADPH oxidase subunits was associated with increased cGMP and phosphorylation of vasodilator-stimulated phosphoprotein at Ser239, suggesting an important role of cGMP-protein kinase G signaling in reduction of anxiety

Bay 60-7550 is a potent and selective inhibitor of 3’,5’-cyclic nucleotide phosphodiesterase type 2 (PDE2) with IC50 value of 4.7 nM for human recombinant PDE2. It is 50-fold more selective for PDE2 compared to PDE1 and greater than 100-fold selective compared to PDE5 PDE3B, PDE4B, PDE7B, PDE8A, PDE9A, PDE10A, and PDE11A. Among the 11 families of PDEs, PDE2 can hydrolyse both cAMP and cGMP and control the levels of both them in the areas which are important for memory formation and storage. In cultured rat cortical neurons and hippocampal neurons, the combination therapy of Bay 60-7550 (1 nM – 1uM) and Bay 41-8543 (1 uM) resulted in significant increase of cGMP levels at concentrations as low as 1nM (compared to incubation with Bay41-8543 alone), reaching levels 20-times base line at 100 nM.