PHARMACOLOGICAL ACTION 



reduced its estimates to 20, 12, 15 and 11 mg. per day.' In Japanese 

 prisoner of war camps nicotinic acid deficiency was common with 

 diets supplying 4 to 6 mg. per day. A marginal intake of 7 to 9 mg. 

 per day was usual in the liberated towns of Western Europe in 1944-45.'' 

 The actual intake of nicotinic acid in the United Kingdom during 

 the war years increased steadily from 13-5 in 1939 to 15-5 in 1944 

 followed by a fall and then a rise to 167 mg. per day in 1947.® 



References to Section 12 



1. E. Kodicek, Lancet, 1942, 1, 380. 



2. A. E. Schaefer, J. M. McKibbin and C. A. Elvehjem, /. Biol. 



Chem., 1942, 144, 679. 



3. S, G. Smith, R. Curry and H. Hawfield, /. Nutrition, 1943, 26, 341. 



4. G. M. Briggs, R. C. Mills, C. A. Elvehjem and E. B. Hart, Proc. 



Soc. Exp. Biol. Med., 1942, 61, 59. 



5. E. H. Hughes, /. Animal Sci., 1943, 2, 23 ; R. W. Luecke, W. N. 



McMillen, F. Thorp and C. TuU, /. Nutrition, 1948, 36, 417. 



6. J. G. Wooley and W. H. Sebrell, /. Nutrition, 1945, 29, 191. 



7. J. C. Drummond, " Nutritional Requirements of Man in the Light 



of Wartime Experience ", Royal Institute of Chemistry, 1948. 



8. " Food Consumption Levels in the United Kingdom ", Cmd. 7203. 



H.M.S.O., 1947. 



13. PHAR2VIACOLOGICAL ACTION OF NICOTINIC ACID 



The toxicity (LD50) of nicotinic acid for rats has been variously 

 reported as 3-5,^ 4-0 to 7-0, ^ 5-0 ^ and 375 mg.^ per kg. ; for mice, 

 the corresponding values are 4-5,^ 4-0 to 7-0^ and 4-5 mg. per kg.^ 

 The toxicity of nicotinamide was higher, the value of LD50 for rats 

 being i-68 ^ or 1-50,* and the value for mice 175 mg. per kg. 



Both compounds had a stimulant action on the central nervous 

 system, and mice developed " morphia tail " and jumped like kan- 

 garoos ; lethal doses caused convulsions.^ Nicotinamide did not 

 increase the work output of the perfused frog gastrocnemius muscle,^ 

 and nicotinic acid had no effect on the isolated normal heart. ^ In the 

 case of failure of the myocardium, however, nicotinic acid brought 

 about a marked increase in the amplitude of the cardiac excursion, 

 reversed the abnormal rhythms and at times increased the coronary 

 flow considerably.^ It was suggested that the observed disturbances 

 of myocardial action were due to inactivation or depletion of pyridine 

 nucleotides by the anoxia, and that the addition of nicotinic acid to 

 the perfusion fluid remedied the deficiency. Rats treated with nico- 

 tinic acid or amide survived a reduction of atmospheric pressure 

 equivalent to a height of 53,800 feet ; untreated rats succumbed at a 

 18 273 



