696 THE BIOCHEMISTRY OF B VITAMINS 



of Lactobacillus acidophilus; the inhibition index was found to be ap- 

 proximately 1900. 



Sarett and Cheldelin 79 observed that pyrithiamine, 2-methyl-4-amino- 

 pyrimidine and 2-methyl-4-amino-5-ethoxymethylpyrimidine inhibit the 

 utilization of either thiamine pyrophosphate or thiamine phosphate more 

 effectively than the utilization of thiamine for growth of Lactobacillus 

 fermentum and Penicillium digitatum. The possibility that dephospho- 

 rylation of the pyrophosphate was inhibited by the analogues and that 

 some thiamine in the free form was essential for growth was considered, 

 but small amounts of thiamine did not affect the inhibition by the ana- 

 logues of the utilization of larger amounts of the pyrophosphate. On the 

 basis of these results, it was suggested that thiamine is attached to the 

 apoenzyme before phosphorylation. 



In 1943, Woolley and White 82 reported that the feeding of pyrithia- 

 mine to mice induced characteristic polyneuritic symptoms of thiamine 

 deficiency, whereas the animals merely lost weight and died without 

 polyneuritic symptoms on a low-thiamine diet. The effect could be pre- 

 vented or reversed by the administration of thiamine; about forty moles 

 of the pyrithiamine nullified one mole of thiamine. Emerson 83 obtained 

 similar results after administering pyrithiamine to rats. In this case also, 

 the inhibition index was approximately 20. 



Wilson and Harris 83a have recently pointed out that repeated analyses 

 of pyrithiamine hydrobromide, which had been assigned the formula 

 Ci4H 2 oN 4 OBr2, gave values which did not correspond closely to this 

 formula. Furthermore, the nitrogen values on different samples were 

 inconsistent. These authors report the preparation of a compound whose 

 constants do correspond to this formula, and the new compound has been 

 named neopyrithiamine. In rats its activity in inhibiting thiamine hydro- 



CH,-^ ^-NH 2 HBr 



CH 3 CH 2 CH 2 OH 

 neopyrithiamine hydrobromide 



chloride is four times as great as that of pyrithiamine. Rabinowitz and 

 Snell 83b have shown that neopyrithiamine alleviates the growth inhibi- 

 tion observed in yeast grown in the absence of vitamin B 6 , but in the 

 presence of thiamine. It is concluded that neopyrithiamine acts as a com- 

 petitive inhibitor to overcome the toxic effect of the added thiamine. 



Although oxythiamine, the 4'-hydroxy analogue of thiamine, is reported 

 to have 0.5 per cent of the antineuritic activity of thiamine for pigeons, 50 



