Species differences in the metabolicC- andN-oxidation, andN-methylation of [¹⁴C]pyridinein vivo

Abstract

1. The metabolism of [2,6-14C]pyridine in vivo has been investigated in the rat, hamster, mouse, gerbil, rabbit, guinea-pig, cat and man, and the quantitative determination of the various urinary metabolites carried out by radiochromatographic analysis. 2. Unchanged pyridine and its N-methylated metabolite, N-methylpyridinium ion, were determined using a Partisil-10 SCX cation-exchange h.p.l.c. column, whereas the C- and N-oxidation products were assayed by reverse-phase chromatography, using a Partisil-10 ODS column. 3. Most of the species studied produce pyridine N-oxide, N-methylpyridinium ion, 2-pyridone, 3-hydroxypyridine and 4-pyridone as metabolites, but the proportion of the dose excreted as each of these metabolites is species-dependent.

Reactions of Sulphate Radicals with Substituted Pyridines: A Structure–Reactivity Correlation Analysis

“…[10] The study of the reactivity of pyridine substrates with SO 4 C À radicals, and the characterization and reactivity of the organic radicals thus generated are of environmental and biological interest, since oxidation of pyridine derivatives is linked to many metabolic processes. [11,12] A correlation of the kinetic behavior of the different substituted pyridines with their chemical structure should bring some light to the role played by the pyridinic moieties in the radical-sensitized oxidation of biological molecules and insecticides. [13] Photolysis of S 2 O 8 2À with excitation wavelengths l exc < 300 nm, Reaction (1), is a clean source of sulphate radical ions with high quantum yields, independent of pH in the range of 3-14.…”

NTP Technical Report on the Toxicity Studies of o-Chloropyridine (CASRN 109-09-1) Administered Dermally and in Drinking Water to F344/N Rats and B6C3F1/N Mice

“…Less than 1% of the recovered 14 C eluted at the retention time for the parent compound suggesting significant metabolism of o-chloropyridine following oral gavage administration. Based on the metabolism of other pyridines [63][64][65] , the urinary excretion of several metabolites was anticipated. Metabolism may include C-and N-oxidation with some conjugation possible.…”

N‐Oxidative Transformations ofCNGroups as Means of Toxification and Detoxification

“…The pyridyl nitrogen is a likely target for electrophilic enzymatic oxidation because of its relatively high electronegativity and its unshared pair of electrons. Indeed, urinary excretion of pyridine N-oxide (40) has been observed after intraperitoneal administration of pyridine to mice, hamsters, rats, guinea-pigs, rabbits, cats and man 7,18,57 ; the N-oxide accounted for up to 40% of the administered dose in some species 18 . In studies on the in vitro N-oxidative transformation of pyridine, 40 was isolated from hepatocytes and subcellular fractions from the livers and lungs of various mammals incubated with the parent amine 28,29,41,56,58 60,92,93 .…”

“…Interest in the role of oximes and nitrones in drug metabolism was enhanced upon the discovery of the occurrence of these N-oxy compounds as intermediates in the hepatic turnover of amphetamines 5,6 eliciting stimulant actions in the central nervous system. Pyridine, bearing a CDN group as part of a heteroaromatic nucleus, is an industrial chemical used as a solvent and as an intermediate in the synthesis of pharmaceuticals, paints and insecticides and has been detected to be metabolically converted to the N-oxide by various animal species 7 , as is also the case with some aromatic diazines 8,9 . Particular accounts on the biochemistry and pharmacology of N-oxygenation of endogenous and exogenous compounds containing CDN group(s) have not been previously given. The present chapter thus undertakes to collate available data on this subject.…”

“…The class of heteroaromatic amines known to undergo biological N-oxygenation includes pyridine (pK a D 5.2), quinoline (pK a D 4.85), isoquinoline (pK a D 5.14), pyridazine (pK a D 2.33), pyrimidine (pK a D 1.3) and pyrazine (pK a D 0.6) structures 7,9,15,16 . As is evident, basicity of these compounds is highly divergent.…”