Abstract
1. To investigate the fate of orally administered niacytin, urine and faeces of rats given single niacytin doses were examined for nicotinic acid derivatives methylated on the pyridine nitrogen atom, determined as trigonelline. 2. Methods were devised for the extraction of trigonelline from urine and faeces and for its differentiation from N′-methylnicotinamide. 3. A prolonged elevation of the excretion of trigonelline in the urine of rats dosed with niacytin was detected colorimetrically, in contrast with the urinary excretion in control groups given free nicotinic acid or hydrolysed niacytin. The total conversion of the nicotinoyl moiety of niacytin into trigonelline was 30–40%. 4. The identity of this metabolite as trigonelline was established by t.l.c., by its u.v. spectrum and by g.l.c. after conversion into methyl nicotinate. 5. The excretion of Ehrlich-positive substances was also increased in urine after administration of niacytin, the increase being approximately parallel to the trigonelline excretion. 6. No increase in the excretion of trigonelline in faeces was found after administration of niacytin. 7. These results suggest a metabolic path-way for niacytin in the rat involving methylation of the pyridine nitrogen without prior release of free nicotinic acid. This hypothesis explains the absence of biological activity of niacytin. An endogenous source of urinary trigonelline was also demonstrated.
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Selected References
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