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

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.