K134 is an inhibitor of phosphodiesterase 3. The IC50s of K134 for PDE3A, PDE3B, PDE5, PDE2 and PDE4 are 0.1, 0.28, 12.1, >300 and >300 μM, respectively.
GSK1370319A is a potent P2X7 antagonist (IC50 = 3.2 nM). GSK1370319A inhibits ATP-induced increase in IL-1β release and caspase 1 activation in lipopolysaccharide (LPS)-primed mixed glia by blocking assembly of the inflammasome in a pannexin 1-dependent manner. GSK1370319A also inhibits ATP-induced subregion-specific neuronal loss in hippocampal organotypic slice cultures, which is dependent on its ability to prevent inflammasome assembly in glia. Significantly, GSK1370319A attenuates age-related deficits in long-term potentiation (LTP) and inhibits the accompanying age-related caspase 1 activity. We conclude that inhibiting P2X(7) receptor-activated NLRP3 inflammasome formation and the consequent IL-1β release from glia preserve neuronal viability and synaptic activity.