Apothesine, “the hydrochlorid of diethyl-amino-propyl-cinnamate,” is an efficient local anesthetic. It belongs to the procain rather than to the cocain type, that is, it belongs to that type which, while effective for injection anesthesia (especially when combined with epinephrin) is relatively inefficient when applied to mucous membranes. Apothesine may also be used for spinal anesthesia. Its absolute toxicity is less than that of cocain (as 20 is to 15, see table below) but about twice that of procain (as 20 is to 40, see table below). It is non-irritant, is easily soluble and makes a stable solution so that it may readily be sterilized.
The Council took exception to certain claims made by Parke, Davis & Company for their product on the ground that these claims were not supported by acceptable scientific evidence. One of the claims was that Apothesine is applicable in any case in which any other local anesthetic is used. This statement, made in many advertisements, is distinctly misleading as used. When applied to mucous membranes Apothesine is far inferior to cocain and to some other local anesthetics, yet the claim obviously suggests that Apothesine is an efficient substitute for any local anesthetic.
The manufacturers claimed, too, that Apothesine is as potent as cocain. The claim would lead the physician to think that Apothesine had the same anesthetic potency as cocain in solution of equal strength. This statement, so far as it refers to the drug when applied to mucous membranes, is not in accord with the facts and is true for injection anesthesia only when stronger solutions are used. The only support for the claim of equal efficiency appears to be the experiments with intracutaneous injections made by H. C. Hamilton[130] in Parke, Davis & Company’s laboratory. These differed considerably from the results of Sollmann.[131] A further series of experiments were made by Sollmann to compare still further the diverse results previously reported by him and Hamilton. The latest series, while showing considerable variations in the susceptibility of different skin areas, especially toward Apothesine, demonstrated in every case that the efficiency of Apothesine is unmistakably lower than that of cocain, being at best one half. The series also showed that the potency of Apothesine was never greater than procain and averaged considerably below it.
Another claim made for Apothesine which the Council holds is not supported by evidence is that of superior safety. This claim is made on the basis of hypodermic injections in guinea-pigs carried out in the laboratory of Parke, Davis & Company. Such experiments prove little because of the fact—well known to laboratory workers—that the use of rodents in toxicity tests made by injecting a drug into the subcutaneous tissues does not give a reliable index of the relative toxicity of such a drug for man. This is due partly to the peculiar resistance of rodents to poisons and partly to the great importance of the rate of absorption. The organism destroys most local anesthetics so rapidly that the rate of absorption is more important than the absolute dose. The absorption from hypodermic injections into guinea-pigs differs, of course, from that in clinical accidents, especially where the drug has been applied to mucous membranes. One cannot, therefore, reliably estimate the degree of clinical danger on animals.
It has been shown that when toxicity tests of local anesthetics are made on cats these animals seem to respond to the drugs in a manner more closely approximating humans and it is a suggestive fact that the more toxic of local anesthetics, as shown by tests on cats, have been found the most dangerous in clinical use. The absolute toxicity of Apothesine has been measured by Eggleston and Hatcher[132] by the intravenous injection in cats. The fatal doses, in terms of milligrams per kilogram ranged as follows:
| Alypin, Holocain | 10 |
| Beta Eucain | 12.5 |
| Cocain | 15 |
| Apothesine | 20 |
| Tropacocain | 20–25 |
| Stovain | 25–30 |
| Nirvanin | 30–35 |
| Procain | 40–45 |
The absolute toxicity of Apothesine is, therefore, only a little lower than that of cocain, and is twice as great as that of procain. The clinical dangers cannot be predicted by either method, since clinical accidents depend, in most instances, on idiosyncrasies, or the technic of application.—(From The Journal A. M. A., Jan. 24, 1920.)