Myocardial protection with the ATP-sensitive potassium channel openers

摘要: The ATP-sensitive potassium channel (K ATP ) openers (e.g. chromakalim) were originally developed for the treatment of hypertension, primarly due to their potent peripheral vasodilating properties. However, clinical studies have failed demonstrate any advantage these compounds over more established antihypertensive agents. Experimental shown that K may be effective a variety diseases (asthma, urinary incontinence, ischemia etc.) besides hypertension. utility is limited lack tissue selectivity. We direct cardioprotective properties which do not require contribution from vasodilatation. first generation agents offer narrow window safety myocardial can compromise already at risk. Our efforts find with lower degree vasorelaxant potency relative resulted in identification new class (5). Their structure-activity relationships antiischemic activity and efficacy vivo are summarized this review. show an electron withdrawing group C6 benzopyran ring, gem-dimethyl C2, trans-hydroxyl C3, sp3 carbon C3/C4 aryl ring attached nitrogen appear involve opening as structurally distinct blockers abolish cardioproptective effects compounds. Unlike (e.g.., cromakalin), selective administered iv observe efficacy. mechanism does sarcolemmal independent action potential shortening. Progress understanding molecular opportunities future research also discussed article