BAY 73-6691 is an inhibitor of brain penetrant PDE9A.

BAY 73-6691 dose-dependently attenuates oxidative stress induced by Aβ25-35. The BAY 73-6691 dose-dependently alleviates cell viability loss due to Aβ25-35 treatment. The BAY 73-6691 attenuates Aβ25-35-induced increase of apoptosis cells[1]. It is found that when SH-SY5Y cells are cultured by Aβ25-35, a high degree of cell apoptosis is observed, while additional stimulation with BAY 73-6691 causes attenuation of cell apoptosis. BAY 73-6691 at 200 μg/mL almost neutralizes Aβ25-35-induced oxidative damage.

BAY 73-6691 significantly enhances the performance of Aβ25-35-injected mice in learning tasks from 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), and dose-dependently reverses the Aβ25-35-triggered reduction in dwell time by the 10th day post-injection (day 10, F(5,54)=27.360, P<0.001). Furthermore, a 3 mg/kg dosage nearly completely negates the delay in escape-latency observed on days 9 to 10, indicating that BAY 73-6691 mitigates the adverse effects induced by Aβ25-35 injections on these measures. Importantly, BAY 73-6691 does not affect swimming speed, demonstrating that its beneficial effects are not due to changes in motor skills. Similarly, in control (sham) mice, BAY 73-6691 does not impair spatial memory or affect four specified indices, nor does it significantly influence hippocampal neuron apoptosis, underscoring its safety and specificity in targeting Aβ25-35-related cognitive disruptions without altering normal hippocampal function[1].