IC50: 5.7±2.1 μM (Na ⁺ /Ca ²⁺ exchanger)

KB-R7943 mesylate blocks NMDAR-mediated ion currents, and inhibits NMDA-induced increase in cytosolic Ca ²⁺ with IC ₅₀ =13.4±3.6 μM but accelerates calcium deregulation and mitochondrial depolarization in glutamate-treated neurons. KB-R7943 depolarizes mitochondria in a Ca ²⁺ -independent manner. KB-R7943 inhibits 2,4-dinitrophenol-stimulated respiration of cultured neurons with IC ₅₀ =11.4±2.4 μM. In addition to NCX _rev , KB-R7943 dose-dependently and reversibly blocked ion currents elicited by NMDA. KB-R7943 dose-dependently inhibits NMDA-induced increases in [Ca ²⁺ ] _c with IC ₅₀ =13.4±3.6 μM confirming the inhibition of NMDA receptors observed in electrophysiological experiments. _wt RyR1-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 ²⁺ 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 I _hERG and native I _Kr rapidly on membrane depolarization with IC ₅₀ values of ~89 and ~120 nM, respectively, for current tails at ?40 mV following depolarizing voltage commands to +20 mV. I _hERG inhibition by KB-R7943 exhibits both time- and voltage-dependence but shows no preference for inactivated over activated channels.