BI-409306

BI-409306 is a potent and selective phosphodiesterase 9A (PDE9A) inhibitor with IC50 values of 65 and 168 nM for the human and rat enzymes, respectively.{52498} It is selective for PDE9A over PDE2A, -3A, -4B, -5A, -6AB, -7A and -10A and 95 non-PDE targets at 10 µM but does inhibit human PDE1A and PDE1C (IC50s = 1.45 and 1.17 µM, respectively). BI-409306 (0.5 mg/kg), in combination with MK-801, an NMDA receptor antagonist that reduces cGMP levels, increases cGMP levels by 41% in mouse striatal tissue compared with MK-801 alone. BI 406306 enhances long-term potentiation (LTP) in hippocampal slices and reverses MK-801-induced working memory deficits in a T-maze task in mice when administered at doses ranging from 0.007 to 2.5 mg/kg.