BAY 73-6691

BAY 73-6691 ((R)-BAY 73-6691) is a potent, brain penetrant, and selective PDE9A inhibitor^[1]. IC50 & Target:PDE9A^[1] In Vitro: The BAY 73-6691 dose-dependently alleviates cell viability loss due to Aβ_25-35 treatment. It is found that when SH-SY5Y cells are cultured by Aβ_25-35, a high degree of cell apoptosis is observed, while additional stimulation with BAY 73-6691 causes attenuation of cell apoptosis. BAY 73-6691 dose-dependently attenuates oxidative stress induced by Aβ_25-35, and BAY 73-6691 at 200 μg/mL almost neutralizes Aβ_25-35-induced oxidative damage. The BAY 73-6691 attenuates Aβ_25-35-induced increase of apoptosis cells^[1]. In Vivo: BAY 73-6691 dose-dependently improves the acquisition performance in the Aβ_25-35-injected mice on days 7 to 10 (day 7, F_(5,54)=65.153; day 8, F_(5,54)=62.340; day 9, F_(5,54)=37.529; day 10, F_(5,54)=38.624; P<0.001). BAY 73-6691 at 3 mg/kg can almost completely abolish the prolongation of escape-latency on days 9 to 10. BAY 73-6691 dose-dependently elevates the Aβ_25-35-induced decrease of the dwell time on the 10th day post Aβ_25-35 injection (day 10, F_(5,54)=27.360, P<0.001). Results reveal that the Aβ_25-35 injection and BAY 73-6691 treatment cause no influence on the swimming speed. Treatment with BAY 73-6691 does not cause detectable alteration of spatial memory in sham mice. BAY 73-6691 alleviates Aβ_25-35-induced abnormalities of the above indices. The BAY 73-6691 causes no influence on the four indices mentioned above in sham mice. The BAY 73-6691 has no significant effect on the apoptosis of hippocampal neurons in sham mice^[1].