KB-R7943 mesylate blocks NMDAR-mediated ion currents, and inhibits NMDA-induced increase in cytosolic Ca with IC50=13.4±3.6 μM but accelerates calcium deregulation and mitochondrial depolarization in glutamate-treated neurons. KB-R7943 depolarizes mitochondria in a Ca-independent manner. KB-R7943 inhibits 2,4-dinitrophenol-stimulated respiration of cultured neurons with IC50=11.4±2.4 μM. In addition to NCXrev, KB-R7943 dose-dependently and reversibly blocked ion currents elicited by NMDA. KB-R7943 dose-dependently inhibits NMDA-induced increases in [Ca]c with IC50=13.4±3.6 μM confirming the inhibition of NMDA receptors observed in electrophysiological experiments. wtRyR1-HEK 293 pretreated with KB-R7943 (10 μM, 10 min) dissolved in the bulk perfusion exhibited significantly attenuated responses to caffeine. In this regard, KB-R7943 produced more pronounced inhibition of caffeine-induced Ca release elicited by 1 mM compared with 0.5 and 0.75 mM (60 versus 58 versus 37%, p<0.05, respectively). KB-R7943 inhibits both IhERG and native IKr rapidly on membrane depolarization with IC50 values of ~89 and ~120 nM, respectively, for current tails at ?40 mV following depolarizing voltage commands to +20 mV. IhERG inhibition by KB-R7943 exhibits both time- and voltage-dependence but shows no preference for inactivated over activated channels.
Medlife has not independently confirmed the accuracy of these methods. They are for reference only.