2-[(3,4-Dihydro-2-phenyl-2H-1-benzopyran-6-yl)oxy]-5-nitro-pyridine

Biochem/physiol Actions

ORM-10103 is a potent, specific inhibitor of the Na(+)/Ca(2+) exchanger, NCX. The compound ORM-10103 inhibits both inward and outward NCX currents with IC50 values of 780 nM, and 960 nM, respectively. ORM-10103 blocks induced arrhythmias in canine cardiac tissue.

Enzyme inhibitor

This novel and specific sodium/calcium exchanger inhibitor (FW = 348.36 g/mol), also known as 5-nitro-2-(2-phenychroman-6-yloxy)pyridine, significantly reduces both the inward (EC50 = 780 nM) and outward (EC50 = 960 nM) currents of the electrogenic sodium-calcium exchanger (or NCX), without significantly change in the L-type Ca2+ current (or ICaL) or the maximum rate of depolarization (or dV/dtmax), indicative of the fast inward Na+ current. The NCX is widely expressed in different tissues. In heart, NCX plays an important role in calcium ion homeostasis, in excitationcontraction coupling, and in the electrophysiological properties of cardiac myocytes. ORM-10103 does not influence Na+/K+ pump or the main K+ currents of canine ventricular myocytes, but at 3 μM slightly diminishes the rapid delayed rectifier K+ current. Amplitudes of early and delayed afterdepolarizations were significantly decreased by ORM-10103 in a concentration-dependent manner. Such findings suggest that ORM-10103 can abolish triggered arrhythmias and may have antiarrhythmic electrophysiological properties. Other NCX inhibitors include: KB-R7943, SEA0400, SN-6, and YM-244769, but KB-R7943 and SEA-0400 also inhibit the ICaL, leaving the interpretation of their antiarrhythmic effects less certain.