Prevention of Toxicity of Massive Doses of A-methopterin by Gitrovorum Factor.

Abstract

Young mice of the Ak stock were injd. intraperit. with citrovorum factor (CF) and A-methopterin either once in the acute expts. or for 5 days in the chronic studies. The results of these expts. demonstrate that the admn. of CF 15 min. prior to 7-30 times as large a dose of A-methopterin prevented the toxicity of the anti-metabolite at levels ranging from 2-100 times the chronic LD50 (1.9 mg.Ag.). Almost complete protection from a single dose of 250 mg./kg. of A-methopterin was afforded by admn. of 15 mg.Ag- of CF given within 1 hr. before or after the antimetabolite. Results of these and other studies seem to indicate that A.methopterin is a true antagonist of CF rather than of pteroylglutamic acid which is far less effective than CF in preventing A-methopterin toxicity.