Connexin hemichannel inhibitor D4 is an orally available small molecule inhibitor of connexin hemichannels (Cx hemichannel).
D4 inhibits the Cx hemichannels but notCx gap junctions using the pilocarpine mouse model of temporal lobe epilepsy (TLE).
D4 caused a near-complete reduction in the pilocarpine-induced cell membrane permeability associated with increased Cx hemichannel activity in vitro.
D4 effectively reduced neuroinflammation and altered synaptic inhibition, which then enhanced the animal survival rate in vivo.
D4 has prolonged effects on suppressing the activation of astrocytes and microglia and rescued the changes in neuroinflammatory and synaptic gene expression induced by pilocarpine in vivo.
