Experimental studies on the mode of action of cardiac glycosides as well as digitalis leaves, with special reference to the rate of detoxication

Experimental studies on the mode of cardiac action of cardiac glycosides, as well as digitalis leaves, notably digicorin, were carried out, employing the pigeon and cat. The duration of action was significantly varied among them, finding the longest in digitoxin. This was followed by digoxin, lanatosid C, some of digitalis leaves, digicorin, ouabain and digitoxigenin in the order herewith given. The onset of the action was proved most rapid with digitoxigenin, followed by digicorin, ouabain, lanatosid C, digoxin, some of digitalis leaves and digitoxin, the last of them showing very much slower than the others. Some differences of mode of action of these glycosides were shown in the experiments in which the activities on the papillary muscle and the changes on the electrocardiogram of them were observed. On the papillary muscle performed by means of Cattell's method, the slight decrease of the threshold of the muscle to the electrical stimulation was followed by the increase of that of the same to it prior to the significant increase of the contraction of the muscle in all drugs tested except digitoxin, while the changes took place in the reversed order in only digitoxin: In comparison with the concentration of those drugs indicating the efficacy and also the toxicity on the papillary muscle digitoxigenin was fairly superior to its parent compound, digitoxin. In view of the fact that the former has been by no means satisfactory in its cardiotonic activities tested in the intact animal, this discrepancy must be interpreted by the evidences that digitoxigenin is much more rapidly metabolized than its parent compound; digitoxigenin is hardly maintained for a certain interval in the concentration enough to bring about its remarkable cardiac actions. The electrocardiogram of the cat revealed that a toxic dose of these drugs except digitoxin caused the depression of the conduction prior to affecting the S-T segment, whereas digitoxin showed the initial change of the S-T segment in the early stage.