Alternative strategies in arrhythmia therapy: Evaluation of Na/Ca exchange as an anti-arrhythmic target

Ca2+ Regulation of Ion Transport in the Na+/Ca2+ Exchanger

“…Although experiences with these inhibitors are overall rather positive, thorough testing in relevant preclinical models remains to be performed (79).…”

Prevention of intracellular calcium overload by blocking NCX

“…In a range of preclinical studies, especially under moderate ischaemia, reverse mode inhibition of NCX has been found to suppress both [Na + ]i and [Ca 2+ ]i overload, hypercontracture, enzyme release and cell damage [35]. Consequently, the inhibition of NCX may have substantial therapeutic potential in the prevention of cardiac ischaemia/reperfusion-induced arrhythmias and injuries [36].…”

Characterization of different aspects of selective NCX inhibition in the heart

“…The ORM-10103 (10) and ORM-10962 (26) are recently synthesised, novel NCX inhibitors having an appropriate selectivity profile to investigate the NCX function (for details see the chapter 1.3). The antiarrhythmic effect of selective NCX inhibition is controversial in the literature (43). NCX inhibitors have shown antiarrhythmic effects in hearth rhythm disturbances evoked by ischemia/reperfusion injury in vivo (44), in Langendorff perfused hearts (45)(46)(47)(48)(49)(50)(51), and in pharmacologically simulated ischemia/reperfusion models (52)(53)(54)(55)(56).…”

“…Benzyloxyphenyl derivative inhibitors like KB-R7943, SEA0400, SN-6 were used successfully in several NCX studies (43). These compounds inhibit NCX from the external side.…”