526 2. ANALOGS OF ENZYME REACTION COMPONENTS 



no permanent effect on the tissue thiamine-PP levels. An important obser- 

 vation was that pyrithiamine induces a more rapid depletion of tissue thia- 

 mine-PP than does elimination of exogenous thiamine. A comparison be- 

 tween dietary deficiency and pyrithiamine administration in rats was report- 

 ed by de Caro et at. (1954). The results in the accompanying tabulation were 



Total thiamine content (//g/g) 



Tissue 



Controls Avitaminotic Pyrithiamine-fed 



Liver 7.42 2.82 1.33 



Muscle 1.60 0.80 0.71 



Brain 3.38 2.89 0.57 



obtained from rats injected with 5 mg pyrithiamine daily for 5-6 days and 

 rats subjected to a thiamine-free diet for a comparable time. In all cases 

 pyrithiamine produces a greater effect than simple elimination of thiamine 

 intake; the effect in brain is particularly striking and possibly correlated 

 with the polyneuritic symptoms produced by pyrithiamine. 



Oxythiamine, on the other hand, does not seem to be so active in reducing 

 the tissue levels of thiamine-PP (Steyn-Parve, 1954). This analog at 1 mg/ 

 day for 15 days to pigeons produces the changes summarized in the accom- 

 panying tabulation. No deficiency symptoms were noted and none would 



Thiamine-PP content (fig/g) 



Tissue 



Controls Oxythiamine-fed % Change 



Heart 

 Muscle 

 Cerebrum 

 Liver 



be expected at these tissue levels. The author believed that the change in 

 the liver is not significant; it is also possible that the large drop in the heart 

 thiamine-PP is too great, since in another experiment with twice the above 

 oxythiamine dosage the level decreases only 34%. The relative ineffective- 

 ness of oxythiamine was confirmed by de Caro et al. (1956) in mice, where 

 0.5-2 mg/day certainly produces little effect on the thiamine levels in muscle 

 and brain, although some decrease in liver is observed. There are likewise no 

 significant change in blood pyruvate. These results were confirmed and ex- 

 tended by Gurtner (1961), who administered pyrithiamine at 250 /yg/day 



