Overview
- Decking, U. K. et al. (1998) Naunyn. Schmiedebergs. Arch. Pharmacol. 358, 547.
- Hartmann, M. et al. (1998) Naunyn. Schmiedebergs. Arch. Pharmacol. 358, 554.
- Ver Donck, L. et al. (1993) Cardiovasc. Res. 27, 349.
- John, G.W. et al. (2004) Cardiovasc. Drug Rev. 22, 17.
- Tamareille, S. et al. (2002) J. Cardiovasc. Pharmacol. 40, 346.
Alomone Labs KC 12291 hydrochloride inhibits NaV1.7 channels expressed in HEK293 cells.A. Time course of current reversible inhibition by 50 μM KC 12291 hydrochloride (#K-105). Currents were elicited by a voltage ramp from a holding potential of -100 mV to 60 mV (30 ms) delivered every 10 seconds. B. Example traces of current response to voltage ramp stimulation before and during 50 μM KC 12291 hydrochloride application.
The pathophysiological importance of Na+ overload is highlighted by the fact that a variety of drugs reducing Na+ influx proved to be cardioprotective, both at the intact organ and cellular level. In addition, a correlation between the degree of Na+ channel blockade and functional recovery from myocardial infarction is established1.
KC 12291 is an orally active atypical voltage-gated sodium channel blocker with cardioprotective properties2-4. It effectively blocks cardiac voltage-gated sodium channels, involving inhibition of the peak Na+ current and thus delays Na+ overload during ischemia by enhancing the inexcitability of the heart4-5.
KC 12291 abolishes diastolic contracture in isolated myocytes obtained from guinea-pig atria, with IC50 values of 0.55 and 0.79 μM respectively, and the IC50 for KC 12291 inhibition of the sustained component of Na+ current, INaL, is 9.6 μM6.
KC 12291 exerts a potent bradycardic effect in the rat7.
