title: (R)-ACX, a pancreatic beta-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 beta-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 beta-cell selective sulfonylurea which, unlike glibenclamide, does not aggravate cardiac ischemia-reperfusion damage.
authors.affiliation: Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Funabashi, Chiba 274-8510, Japan.
authors.forename: Iyuki
authors.initials: I
authors.lastname: Namekata
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Shuhei
authors.initials: S
authors.lastname: Moriguchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Terasawa
authors.forename: Reiko
authors.initials: R
authors.lastname: Yamagishi
authors.forename: Tokiko
authors.initials: T
authors.lastname: Aikawa
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Saito
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kurashima
authors.forename: Kenji
authors.initials: K
authors.lastname: Seri
authors.forename: Yorishige
authors.initials: Y
authors.lastname: Imamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Akita
authors.forename: Koki
authors.initials: K
authors.lastname: Shigenobu
authors.forename: Hikaru
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005905:Glyburide / Q000494:pharmacology / Q000633:toxicity; D006168:Guinea Pigs; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000633:toxicity; D066298:In Vitro Techniques; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D010210:Papillary Muscles / Q000187:drug effects; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D001578:Benzopyrans; D005905:Glyburide; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C406484:4-(1-acetoxyethyl)-N-(cyclohexylcarbamoyl)benzenesulfonamide; D000096926:Benzenesulfonamides; C427584:NIP142