Comparative study of the antiarrhythmic activity of L-, D-and DL-stereoisomers of potassium magnesium aspartate

摘要

Injection forms of potassium (K) and magnesium (Mg) aspartate (Asp) were compared in preventing cardiac disorders caused by electrolytic disturbances, primarily low K and Mg levels (e.g. caused by the treatment with cardiac glycosides and diuretic drugs). Widely used K- and Mg-Asp preparations (asparkam, panangin, pamaton) are synthesized from aspartic acid representing a racemic mixture of L- and D-stereoisomers. Differences in metabolism and utilization of D- and L-amino acids probably influence the pharmacological properties of K and Mg L- and D-aspartates. Moreover, the pharmacologically effective doses of Mg and K salts can induce toxicity, which depends on the nature of anions. The aim of this study was to compare of antiarrhythmic action of K and Mg L-, D-, and DL-Asp stereoisomers using calcium chloride (CaCl2) and aconitine induced arrhythmia models in rats and strophanthin-K induced arrhythmia model in guinea pigs. It was found that intravenously administered K- and Mg-L-Asp exhibited higher activity compared to K- and Mg-D- and DL-Asp on the strophanthin-K, CaCl2, and aconitine induced arrhythmia models. Indeed, K- and Mg-L-Asp more effectively decreased the incidence of arrhythmias, increased the time to onset of the first arrhythmia, decreased percentage loss of rats, and increased the survival life of animals after the first arrhythmia onset in rats with arrhythmias induced by strophanthin-K and CaCl2 as compared to K and Mg-D- and DL-Asp. At the same time K- and Mg-L-Asp was better than D- and DL-Asp with respect to acute toxicity (LD50), effective dose (ED50) and antiarrhythmic (therapeutic) ratio (LD50/ED50) in rats with aconitine-induced arrhythmia model.