Species variations in theN-methylation and quaternization of [14C]pyridine

Publisher Website
Google Scholar
Abstract
1. The quaternization of [14C]pyridine by metabolic N-methylation in vivo has been investigated in eight species by determination of the urinary excretion product, N-methylpyridinium. 2. All eight species N-methylated pyridine, but the extent to which this occurred was species-dependent; methylation was extensive (20–40% dose) in the cat, guinea-pig, gerbil. rabbit and hamster, but was low (5–12% dose) in rat, mouse and two human volunteers. The low N-methylation in the rat was not enhanced by dl-methionine supplementation. 3. In the rat and guinea-pig, the pattern of N-methylation was similar when the [14C]pyridine was given by the oral and intraperitoneal routes. In both species the reaction was dose-dependent. 4. N-Methylpyridinium excretion was found to be a valid parameter of the N-methylation of pyridine in vivo, since rats and guinea-pigs eliminated this compound in the urine unchanged following its intraperitoneal administration. 5. The pharmacological and toxicological implications of the biological quaternization of azaheterocycles are discussed.

This publication has 14 references indexed in Scilit: