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.
NCI-Frederick Cancer Research Facility, BRI-Basic Research Program, MD 21701.
S S
SS
Singer
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W
Lijinsky
L E
LE
Kratz
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N
Castagnoli
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JE
Rose
D000631:Aminopyridines / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D005966:Glucuronidase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008701:Methapyrilene / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains
D000631:Aminopyridines; D008701:Methapyrilene; D005966:Glucuronidase