ANALOGS OF THIAMINE 527 



and oxy thiamine at 10 mg/day to rats intraperitoneally for 29 days; a 

 thiamine-deficient group was also included (see accompanying tabulation). 



The differences in the actions of the two analogs is well illustrated here; 

 pyrithiamine produces marked neurological symptoms without much effect 

 on weight, cardiac rate, or blood pyruvate, although there is a very signi- 

 ficant fall in tissue thiamine-PP, whereas oxythiamine causes bradycardia 

 and weight loss without neurological effects, while the blood pyruvate is 

 elevated greatly without significant changes in tissue thiamine-PP. 



Tissue Levels of Pyrithiamine 



The pyrithiamine in rat tissues following the injection of 1 mg intraperi- 

 toneally was determined microfluorimetrically by Rindi and Perri (1961) 

 and Rindi et al. (1961) and the results are plotted in Fig. 2-18. These rats 

 had been maintained on a thiamine-deficient diet and within 1 day the pyri- 

 thiamine content of the tissues corresponded closely to the normal thiamine 

 content, indicating that the analog probably occupies the binding sites nor- 

 mally occupied by thiamine or its diphosphate. It was also shown that prac- 

 tically all of the pyrithiamine in the liver is phosphorylated. The concen- 

 tration in the brain increases progressively throughout the 12 days of the 

 experiment and it is likely that this reflects a transference of pyrithiamine 

 from the liver, the analog gradually replacing the thiamine in the brain. 

 Daily oral administration of 33 //g thiamine and 210 //g pyrithiamine leads 

 to a slow but very definite rise in tissue pyrithiamine over 20 days, the levels 

 eventually reached being higher than following the single intraperitoneal 

 injection. It is unfortunate that we have no data on oxythiamine distribu- 

 tion in the tissues, since this might well help to answer some of the problems 

 as to why its effects are often quite different from those of pyrithiamine. 



