New trends in the development of oral antidiabetic drugs

Valeria Kecskemeti; Zsolt Bagi; Pal Pacher; Ildiko Posa; Erzsebet Kocsis; Maria Zs Koltai

doi:10.2174/0929867023371427

New trends in the development of oral antidiabetic drugs

Valeria Kecskemeti, Zsolt Bagi, Pal Pacher, Ildiko Posa, Erzsebet Kocsis, Maria Zs Koltai

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

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 everyday 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 μmol/kg) according to their cardiovascular activity in healthy and diabetic animals. In vitro (1-100 μmol/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.

Original language	English (US)
Pages (from-to)	53-71
Number of pages	19
Journal	Current Medicinal Chemistry
Volume	9
Issue number	1
DOIs	https://doi.org/10.2174/0929867023371427
State	Published - 2002
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Drug Discovery
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2174/0929867023371427

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title = "New trends in the development of oral antidiabetic drugs",

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 everyday 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 μmol/kg) according to their cardiovascular activity in healthy and diabetic animals. In vitro (1-100 μmol/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 KATP 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.",

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AU - Koltai, Maria Zs

PY - 2002

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New trends in the development of oral antidiabetic drugs

Abstract

ASJC Scopus subject areas

UN SDGs

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