(R)-ACX, a pancreatic beta-cell selective sulfonylurea, does not aggravate myocardial ischemia-reperfusion damage.
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.
Namekata
Iyuki
I
Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Funabashi, Chiba 274-8510, Japan.
Yamaguchi
Yusuke
Y
Moriguchi
Shuhei
S
Yamazaki
Satoshi
S
Terasawa
Akihiko
A
Yamagishi
Reiko
R
Aikawa
Tokiko
T
Saito
Tomoaki
T
Kurashima
Katsumi
K
Seri
Kenji
K
Imamura
Yorishige
Y
Akita
Hiroyuki
H
Shigenobu
Koki
K
Tanaka
Hikaru
H
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
D001578:Benzopyrans; D005905:Glyburide; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C406484:4-(1-acetoxyethyl)-N-(cyclohexylcarbamoyl)benzenesulfonamide; D000096926:Benzenesulfonamides; C427584:NIP142