N-debenzylation of pyrilamine and tripelennamine in the rat. A new metabolic pathway.
Male Sprague-Dawley rats received 20 mg/kg of pyrilamine or tripelennamine intraperitoneally. The extract obtained from an enzymatically hydrolyzed urine was derivatized with or without Tri-Sil Z and analyzed by GC/MS. 2-(2-Dimethylaminoethyl)aminopyridine, 2-(4-hydroxybenzyl)aminopyridine, 2-[4-hydroxybenzyl-(2-dimethylaminoethyl)amino]pyridine, 2-[4-hydroxybenzyl-(2-methylaminoethyl)amino]pyridine, 2-[4-hydroxy-3-methoxybenzyl-(2-dimethylaminoethyl)amino]pyridine, and 2-[3-hydroxy-4-methoxybenzyl-(2-dimethylaminoethyl)amino]pyridine were detected as metabolites of pyrilamine. 2-(2-Dimethylaminoethyl)aminopyridine, 2-(alpha-hydroxybenzyl)aminopyridine, 2-[alpha-hydroxybenzyl-(2-dimethylaminoethyl)amino]pyridine, 2-[4-hydroxybenzyl-(2-dimethylaminoethyl)amino]pyridine, 2-[4-hydroxy-3-methoxybenzyl-(2-dimethylaminoethyl)amino]pyridine, and 2-[3-hydroxy-4-methoxybenzyl-(2-dimethylaminoethyl)amino]pyridine were detected as metabolites of tripelennamine. Thus, N-debenzylation of tripelennamine and N-demethoxybenzylation of pyrilamine occurs in vivo, through an intermediate of alpha-carbon oxidation and represents a new metabolic pathway for these compounds. The identity of the metabolite was confirmed by comparison with an authentic sample of 2-(2-dimethylaminoethyl)aminopyridine. The pharmacological implication of 2-(2-dimethylaminoethyl)aminopyridine, one of the metabolites of pyrilamine and tripelennamine, is discussed.
D000631:Aminopyridines / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002855:Chromatography, Thin Layer; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D011738:Pyrilamine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014309:Tripelennamine / Q000378:metabolism*
D000631:Aminopyridines; D014309:Tripelennamine; D011738:Pyrilamine