A comparison of in vivo and in vitro metabolites of the H1-antagonist N,N-dimethyl-N'-2-pyridyl-N'-(2-thienylmethyl)-1,2-ethanediamine (methapyrilene) in the rat.

1. The H1-antagonist N,N-dimethyl-N'-2-pyridyl-N'-(2-thienylmethyl)-1,2-ethanediamine (methapyrilene) is carcinogenic in rats. 2. The compound, which is inactive in short-term tests and does not bind to DNA, has been classified as a non-genotoxic carcinogen. 3. Studies have been made in vitro and in vivo in F344 and Sprague-Dawley rats. New metabolites included N-(N',N'-dimethylaminoethyl)-2-aminopyridine and the corresponding N'-oxide, a derivative in which methapyrilene is hydroxylated on the 5-position of the pyridine ring, 2-(N',N'-dimethylamino)-N-2'-pyridylacetamide, N-(2-pyridyl)-N-2"-thienylmethyl)aminoacetaldehyde, and 2-hydroxymethylthiophene. 4. Both strains of rat metabolize methapyrilene to reactive species which may be of importance in the carcinogenic process.