Cloetta reported the result of an elementary analysis of his product which he compared to the analyses of digitoxin (crystalline) made by Schmiedeberg and by Kiliani, and stated that there could be no doubt concerning the chemical identity of the two substances.
Kiliani[29] characterized as preposterous Cloetta’s claim that the active constituent of Digalen is chemically identical with digitoxin and stated that Digalen was merely an impure digitalein. Kiliani has recently reiterated the statement that the so-called “amorphous digitoxin” is not identical with digitoxin.[30]
Cloetta’s failure to publish his method of preparing Digalen places an additional burden of proof on him (or the manufacturers of Digalen), concerning the identity of the product, and in the face of Kiliani’s denial of the correctness of Cloetta’s contention we must have strong corroborative evidence of Cloetta’s claim before we can accept it as being established.
The difficulties of dealing with the chemistry of digitalis are so well known that they hardly require further mention here, but under the circumstances Cloetta cannot be considered as being wholly unprejudiced, and, while the same might perhaps be said of Kiliani, such evidence as can be deduced tends strongly to support Kiliani’s view, and to disprove the contention of Cloetta.
There is much confusion regarding the names which have been applied to the various principles obtained from digitalis, and while it is undesirable that an established name should be given to a newly discovered principle, one might overlook this if no effort were made to associate the therapeutic actions of the two substances to an extent which the truth did not justify.
While the Council at that time did not challenge the existence of “amorphous digitoxin” and made no attempt to determine the identity with digitoxin of the substance forming the basis of Digalen, the manufacturers of Digalen have sought to show that Digalen and digitoxin were identical so far as their therapeutic actions were concerned, but that Digalen lacked the disadvantages of digitoxin. What was a purely academic question when the acceptance of Digalen was under discussion by the Council becomes a matter of very great practical importance when the manufacturers of Digalen seek to mislead the physician by these claims.
The evidence which lends support to the view that Digalen and digitoxin are wholly dissimilar may be summarized as follows: Digalen differs greatly in its physical properties from digitoxin and in certain of its physiologic actions, as the manufacturers themselves state, Digalen being amorphous, and soluble in water, while digitoxin is crystalline and insoluble in water. The manufacturers state that Digalen differs from digitoxin in certain of its physiologic actions, but the two substances do indeed differ far more than they admit.
Cloetta and the manufacturers of Digalen lay especial stress on the claim that Digalen is cumulative to a far less extent than digitoxin, and that it has far less tendency to cause gastric disturbance than the latter. The first of these claims is true; the second is the very opposite of the truth, as we shall show.
We know nothing of the structure of any of the digitalis principles, and even though one were to admit (purely for the sake of argument) that Digalen and digitoxin were chemical isomers, that fact could not be taken to lend any support to the contention that the two substances were identical, in the face of the established fact that they differ physically and physiologically in nearly every particular, and agree only in that they both cause standstill of the heart in the same way—an action possessed also by so dissimilar a substance as barium.