THE FOLIC ACID COMPLEX 



2h. J. R. Totter, W. E. Martindale, M. McKee, C. K. Keith and P. L. 

 Day, Proc. Soc. Exp. Biol. Med., 1949, 70, 435. 



3. J. M. Cooperman, C. A. Elvehjem, K. B. McCall and W. R. Rue- 



gamer, ihid., 1946, 62, 92. 



4. L. S. P. Davidson and R. H. Girdwood, Brit. Med. J., 1947, ^' ^^T- 



5. C. F. Asenjo, /. Nutrition, 1948, 36, 601. 



6. S. J. Darke and C. White, Brit. J. Nutrition, 1948, 2, ix. 



7. M. B. Williamson, Proc. Soc. Exp. Biol. Med., 1949, 70, 336. 



14. PHAR2VIACOLOGY OF FOLIC ACID 



Pteroylglutamic Acid 



The pharmacological properties of pteroylglutamic acid were 

 described by Harned et al.'^ The acute intravenous toxicity was 

 very low, the following values being obtained for LD50 : mice, 600 ; 

 rat, 500 ; rabbit, 410 ; guinea-pig, 120 mg. per kg. of bodyweight. 

 In the rat, most of the deaths occurred within thirty minutes of the 

 injection, and followed a violent convulsion, which was mainly toxic. 

 In rabbits and guinea-pigs many of the deaths were delayed and in 

 these instances were due to renal damage, pteroylglutamic acid being 

 precipitated in the tubules. Male mice tolerated dosages that were 

 lethal to females. 2 



When rabbits were given 50 mg. per kg. per day intraperitoneally 

 for ten weeks, there was a possible retardation of growth, but no 

 difference between the treated and control group was observed as 

 regards blood picture, nrnnber of deaths or general appearance. At 

 autopsy, however, the treated group showed signs of renal injury. 

 Similarly in rats given 75 mg. per kg. per day intraperitoneally, 

 growth was slightly depressed but no other effect was observed except 

 renal damage. 



Pteroylglutamic acid did not affect the respiration of the dog or 

 cat in doses up to 100 mg. per kg. intravenously, or the rabbit in doses 

 up to 50 mg. per kg. A temporary rise in blood pressure occurred in 

 the dogs following injection and a slight rise or fall in the cats. The 

 substance had no appreciable effect on the rabbit ilemn, it did not 

 affect the blood sugar of fasted rats, produced no irritation when 

 injected intracutaneously into guinea-pigs, and had no diuretic activity. 



Xanthopterine 



The pharmacological properties of xanthopterine were described 

 by H. Horlein.^ He found it to be virtually non-toxic when adminis- 

 tered orally, whilst the lethal dose of the sodium salt given intra- 

 venously was 50 mg. per kg. for mice, 30 mg. per kg. for rabbits and 



508 



