Studies on Cardioactive Steroids

Abstract

In the present paper 32 genins and glycosides were tested for positive inotropic and arrhythmogenic activities at the isolated, spontaneously beating atrium of the guinea pig. It was found that: (a) substituents in C12-OHand C19-OH, respectively, diminished the efficacy 10-to 100-fold; (b) the acetylation at 16α-OH and 16β-OH, respectively, caused a 6- to 8-fold increase of efficacy, and (c) the esterification with acyl acids via hydroxyl groups at the sugar moiety caused a 2- to 10-fold decrease of efficacy depending on structure, number, and volume of the substituents. Similar results were gained with the cardioactive steroids at the (Na⁺-K⁺)-ATPase system and at the muscle tonus of the isolated guinea-pig ileum, demonstrating parallelism between these three parameters.

Studies on Cardioactive Steroids

“…For further details cf. the preceding paper (Haustein, 1973b). Throughout this paper the tested glycosides are denoted with current numbers (in brackets) from table I of this paper.…”

“…the preceding paper (Haustein, 1973b). A, was evaluated by electrocardiographic recordings of each heart in intervals of 5 min during control and test period.…”

“…The data (glycoside con centrations in pM) are plotted in a log-log system. The data of the atrium experiments are taken from Haustein, 1973b. (Fig. 4) Figure 4 shows a significant correlation of the effects of the tested glyco sides in both preparations (r = 0.945, p < 0.01).…”

Studies on Cardioactive Steroids

“…Studies on isolated spontaneously beating guinea pig auricles and on isolated guinea pig hearts were performed as described in previous papers (1,6,8,12). After dissection of both ventricles, the atria were prepared along the cranial and caudal venae cavae.…”

“…Since 16a-gitoxin is effective at relatively high con centrations, more potent glycosides were re searched. According to structure-activity rela tionships in a series of various semisynthetic genins and glycosides, a distinct increase in potency in the isolated heart (1,5) and in preparations of isolated guinea pig ileum (5,7,9) was reached by substitution of the free OH groups in the 16/3-position of the gitoxigenin moiety for acetoxy or nitrate groups. Having these findings in mind, studies on a series of 16a-derivatives were of interest.…”