Influence of Magnesium Salts Upon the Toxicity and Antipyretic Action of the Salicylates.

Abstract

In the preceding paper we have shown that magnesium chlorid is antipyretic to rabbits in hay-infusion fever. Furthermore the antipyretic efficiency of amidopyrin was found considerably potentiated by combination with magnesium chlorid, although in the same combination the toxicity appears slightly decreased.

The synergistic action of magnesium combined with antipyretic drugs is further illustrated by the following experiments upon magnesium combinations with salicylates. The work will be described under 3 heads: (1) toxicity in normal mice of sodium salicylate alone and in combination with MgCl₂; (2) antipyretic action in fevered rabbits of sodium salicylate alone and combined with MgCl₂; (3) antipyretic action in fevered dogs of aspirin alone and in combination with magnesium oxide.

1. Toxicity.

In normal white mice, the m.l.d. (minimal lethal dose) of sodium salicylate was found to be about 600 mg. per kilo (Table I). Similarly, the m.l.d. of a combination of 2 parts sodium salicylate with 3 parts magnesium chlorid (anhydrous) was found to be approximately 975 mg. per kilo (Table II). Our criterion for judging the m.l.d., as will be seen, does not include an occasional fatality within that range of dosage where survival is obviously the rule.

In the previous report, it was shown that the m.l.d. for magnesium chlorid is approximately 1.05 gm. per kilo. Thus the predicted m.l.d. for the present combination with sodium salicylate would be 807.5∗ mg. per kilo. Inasmuch as 975 mg. were, with 1 exception, actually required, there is evidently an antagonism between the 2 drugs favorable to survival. The combination is about 20% less toxic than predicted. This accords with the mutual antagonism shown between many depressant drugs when combined, and is most readily explained by the wider distribution of the loci of toxic action.