( R)-ACX, a pancreatic β-cell selective sulfonylurea, does not aggravate myocardial ischemia-reperfusion damage

Abstract

The organ selectivity and the effect on myocardial ischemia-reperfusion injury of ( R)-acetoxyhexamide (( R)-ACX), a novel sulfonylurea, were examined. ( R)-ACX, as well as glibenclamide, concentration-dependently stimulated insulin release from INS-1 cell, a cell line derived from pancreatic β-cells. The potency of ( R)-ACX was about 1/10 of that of glibenclamide. In isolated guinea pig ventricular myocardial tissue, glibenclamide concentration-dependently inhibited the action potential shortening by NIP-121, an ATP-sensitive potassium channel opener, but ( R)-ACX showed only slight inhibition. In isolated rat aortic rings contracted with norepinephrine, glibenclamide concentration-dependently inhibited the relaxation by NIP-121, while ( R)-ACX showed only slight inhibition. In coronary-perfused guinea pig ventricular preparations, glibenclamide reduced the recovery of contractile force after ischemia-reperfusion, while ( R)-ACX did not. In conclusion, ( R)-ACX is a β-cell selective sulfonylurea which, unlike glibenclamide, does not aggravate cardiac ischemia-reperfusion damage.