Comparison between the Fatal Doses of Drugs for the Mouse and for the Frog, together with the Influence of the Combined Application of Drugs upon their Toxicity

Abstract

Each of forty five different kinds of drugs, including alkaloids, glucocids, toxins, compounds of fatty series, salts of the heavy metals, acids and alkalis were injected in turn into the subcutis of the mouse and the lymph-sac of the frog, and the minimum fatal dose and the surely fatal dose in each case were noted. These experiments were carried on in the summer, extending from the early part of June to the early part of September, under the same conditions. Afterward, the effects of forty nine series of combinations of drugs were observed for the purpose of finding out the changes in toxicity of those drugs, as a result of the combined application.
The following results were obtained:
Strychinin, picrotoxin, caffein, atropin, apomorphin, barium, saponin, cornutinum ergoticum “Bombelon”, calcium, morphin, scopolamin, chloral hydrate, urethan, bromide, antipyrin, pyramidon, cocain, nicotin, pilocarpin, quinine, magnesium, arsenic acid, aqua pruni armeniacae, lobelin, bichloride of mercury, adrenalin, curare, eserin, emetin, aloin, cholic acid and sodium hydroxid showed greater toxicity in the case of mouse than in the case of frog. The most remarkable difference in this respect was observed in eserin, which was 760 times more toxic to the former than to the latter.
Cinchonin, diuretin and hydrochloric acid showed similar toxicity for both kinds of animals, while the fatal doses of the heart stimulants, such as digitalin, strophanthin, scillaren and camphor, as well as of pottasium. veratrin, aconitin, hydrastin aud guanidin for the mouse were larger than for the frog. The widest variation within this group was showh by digitalin which proved to be 22.7 times more toxic to the mouse than to the frog.
Individual differences of resistance to the drugs were recognized in all kinds of drugs and in both kinds of animals. The percentage of differences between the two fatal doses, the minimum and the surely fatal, was, in the case of the mouse 22.15% of the minimum fatal dose and, in the case of the frog, 21.63%, on an average in the forty five kinds of drugs used in the tests.
The different combinations of two kinds of drugs produced various effects such as antagonism, synergism or addition, in some cases, while in other cases no interaction was seen. Such difference in the effects produced was due not only to variation in the drugs or the animals employed, but also to interchange in the proportion of the principal and subordinate drugs used in the combination. The sesults of forty-nine series of combination tests might be grouped as follows;
1) The effects produced by some of the combinations were the same in both kinds of animals. For example. The combination of strycbinin and chloral hydrate (antagonism), of strychinin and morphin (synergism), of picrotoxin and scoporamin (addition) etc.
2) Some combination showed interaction in one kind of animals while no interaction was recognized in other kind of animals. For example. The combination of hydrastin and morphin resulted in synergism, of caffein and arsenic acid in addition in the mouse, but with no interaction in the frog. The combination of curare and guanidin produced antagonism, of adrenalin and atropin produced synergism in the frog, but with no interaction in the mouse.
3) Antagonism was observed in one kind of animals, and addition in the other, For example. The combination of curare and eserin produced antagonism in the mouse and addition in the frog, while adrenalin and pottasium produced addition in the mouse and antagonism in the frog.
4) Synergism in one kind of animals, but simply addition in the other. For example. The combination of strychinin and scopolamin causing synergism in the mouse and addition in the frog, and of curare and nicotin causing addition in the mouse and synergism in the frog.
5) By interchanging the proportion of the drugs used in the combination, different effects were observed. For example.