Absence of exacerbation of myocardial stunning in anesthetized dogs treated with KAD-1229, a novel hypoglycemic agent

The effect of (+)-momocalcium bis[(2S,3a,7a-cis)-alpha -benzylhexahydro-gam ma -oxo-2-isoindolinebutyrate]dihydrate (KAD-1229), a novel hypoglycemic ag ent with a chemical structure different from that of the sulfonylureas, on myocardial stunning was assessed in anesthetized dogs by comparison with th at of glibenclamide, a sulfonylurea. Even though their hypoglycemic effects were of similar magnitude, glibenclamide (1 mg/kg, i.v.), but not KAD-1229 , exacerbated the myocardial stunning induced by occlusion/reperfusion of t he descending coronary artery. In a receptor-binding experiment, unlabeled glibenclamide completely inhibited [H-1]glibenclamide binding to the myocar dium, but KAD-1229 did not. These results suggest that the difference in bi nding properties of KAD-1229 and glibenclamide toward cardiac sulfonylurea receptors is one of the causes of their different effects on myocardial stu nning. It is likely that KAD-1229 is highly specific for pancreatic sulfony lurea receptors and is speculated to be a safer hypoglycemic agent than, at least, glibenclamide. (C) 2001 Elsevier Science B.V. All rights reserved.