title: Investigation of Metabolite Profile of YM758, a Novel If Channel Inhibitor.
abstract: BACKGROUND
  YM758 monophosphate is a novel If channel inhibitor that has an inhibitory action for If current and shows a strong and specific activity, selectively lowering the heart rate and decreasing oxygen consumption by heart muscle.
  
  
  OBJECTIVE
  The objectives of the current study were to investigate the in vivo metabolic profiles of YM758 in mice, rats, rabbits, dogs, and monkeys and to elucidate the structures of YM758 metabolites.
  
  
  METHODS
  Biological samples were analyzed by liquid chromatography hyphenated with a radiometric detection system and liquid chromatography coupled with a mass spectrometer to clarify their metabolic patterns. To elucidate their structures, metabolites were isolated and analyzed by mass spectrometry and nuclear magnetic resonance spectroscopy.
  
  
  RESULTS
  Our results from in vivo metabolic profiling in humans and animals indicated there is no significant species difference in the metabolism of YM758, and the metabolic pathways of YM758 are considered to be oxidation, hydration, and demethylation followed by sulfate or glucuronide conjugation.
authors.affiliation: Analysis and Pharmacokinetics Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., Miyukigaoka 21, Tsukuba, Ibaraki, 305-8585, Japan. naoyuki.nakada@astellas.com.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Nakada
mesh_terms: D000818:Animals; D001549:Benzamides / Q000097:blood / Q000378:metabolism* / Q000652:urine; D001646:Bile; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000037:antagonists & inhibitors*; D007546:Isoquinolines / Q000097:blood / Q000378:metabolism* / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D051379:Mice; D011817:Rabbits; D051381:Rats; D026941:Sodium Channel Blockers / Q000032:analysis / Q000097:blood / Q000378:metabolism* / Q000652:urine; D013045:Species Specificity
chemical_list: D001549:Benzamides; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007546:Isoquinolines; D026941:Sodium Channel Blockers; C530155:YM 758