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

Abstract

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 include 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.