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New trends in the development of oral antidiabetic drugs
Valeria Kecskemeti1, Zsolt Bagi, Pal Pacher
1Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary. KECSVAL@PHARMA.SOTE.HU
Abstract:
A large number of oral antidiabetic agents are available today. This article provides a short review of the pharmacology and some clinical aspects of various oral antidiabetic drugs. It focuses mainly on the newest developing drugs (therapy of the near future) and on the most commonly used older groups for the common approach of every-day practice (sulphonylureas). The primary goal of this review is to compare the electrophysiological effects of glibenclamide in isolated normal and streptozotocin induced diabetic rats and alloxan induced rabbits ventricular preparations, while on the other hand to differentiate the hypoglycaemic sulphonylureas (0.1-1000 mmol/kg) according to their cardiovascular activity in healthy and diabetic animals. In vitro (1-100 micromol/l) as well as chronically treated (5 mg/kg for 10 weeks) glibenclamide prolonged the action potential duration in normal but failed to affect it in diabetic ventricular preparations. Our results suggest that the sensitivity to glibenclamide of K(ATP) channels in diabetic ventricular fibers is drastically decreased. The effects of different sulphonylureas (tolbutamide, glibenclamide, gliclazide, glimepiride) on ventricular ectopic beats as well as the duration of ventricular fibrillation induced by 10 min ischemia/50 min reperfusion in healthy and diabetic rats were compared. Tolbutamide and gliclazide dose-dependently enhanced both parameters both in healthy and diabetic groups. Glibenclamide in healthy rats increased, while in diabetic rats it decreased the arrhythmogenicity. Glimepiride depressed the arrhythmogenicity in both healthy and diabetic animals. Glimepiride proved to dose-dependently enhance the myocardial tissue flow in dog in contrast to glibenclamide. These results confirm that glimepiride has less cardiovascular actions than other sulphonylureas. From the newest oral antidiabetics this review tries to emphasize the most important basic pharmacological properties, mechanism of action, therapeutic use.