ANALOGS OF NICOTINAMIDE 495 



pyridine, other excretory products were investigated and increased urinary 

 nicotinate and various glucuronides were found (Beher and Anthony, 1953). 

 No urinary 3-acetylpyridine could be detected. An interesting suggestion 

 that the oxidation of 3-acetylpyridine may involve NAD(P) enzymes was 

 made; this might mean that in nicotinate-deficient animals, where NAD(P) 

 levels are low, the oxidation of 3-acetylpyridine would be impaired and the 

 analog would be more toxic. 3-Acetylpyridine presents the strange situation 

 wherein the analog is detoxified to the normal metabolite, and this would 

 presumably tend to counteract the inhibitory effects. In low dosage (25- 

 60 mg/day), 3-acetylpyridine can protect against black tongue in dogs but 

 at higher dosage it can create a nicotinate deficiency (McDaniel et al., 1955). 

 Animals may have a limited ability to oxidize 3-acetylpyridine; small 

 amounts are mainly oxidized and little 3-acetylpyridine is left to inhibit, 

 whereas the larger doses exceed the metabolic capacity of the system. This 

 is indicated by the results of Guggenheim and Diamant (1958), who deter- 

 mined the excretion of iV-methylnicotinamide in rats given comparable doses 

 of nicotinamide and 3-acetylpyridine (see tabulation). Beyond a dose of 50 



" Ratio calculated after substracting endogenous excretion. 



mg/kg there seems to be relatively less oxidation of the analog. Adminis- 

 tration of 3-acetylpyridine-C^*H3 to rats leads to 30% of the activity ex- 

 pired as CO2 and 44% eliminated in the urine during 24 hr (Beher et al., 

 1959); since the total dosage was probably around 100 mg/kg, smaller doses 

 might be even more efficiently oxidized. 3- Acetylpyridine is also partially 

 metabolized to NAD and the 3-acetylpyridine analog of NAD, as will be 

 discussed shortly. Finally, nicotinamide mononucleotide excretion is aug- 

 mented by 3-acetylpyridine and it is possible that this mainly originates 

 directly from the analog (McDaniel et al., 1955). The metabolism of 3-acetyl- 

 pyridine and the compounds derived from it thus depend on the species, 

 the dose, and whether the animals are normal or nicotinate-deficient. 



We shall now examine the effects of 3-acetylpyridine on the tissue levels 

 of NAD, the formation of NAD analogs, and the enzymic activities of these 



