Identification of metabolites of a substance P (Neurokinin 1 receptor) antagonist in rat hepatocytes and rat plasma
dc.contributor.author | Hop, C.E.C.A. | |
dc.contributor.author | Wang, Y. | |
dc.contributor.author | Kumar, S. | |
dc.contributor.author | Elipe, M.V.S. | |
dc.contributor.author | Raab, C.E. | |
dc.contributor.author | Dean, D.C. | |
dc.contributor.author | Poon, G.K. | |
dc.contributor.author | Keohane, C.-A. | |
dc.contributor.author | Strauss, J. | |
dc.contributor.author | Chiu, S.-H.L. | |
dc.contributor.author | Curtis, N. | |
dc.contributor.author | Elliott, J. | |
dc.contributor.author | Gerhard, U. | |
dc.contributor.author | Locker, K. | |
dc.contributor.author | Morrison, D. | |
dc.contributor.author | Mortishire-Smith, R. | |
dc.contributor.author | Thomas, S. | |
dc.contributor.author | Watt, A.P. | |
dc.contributor.author | Evans, D.C. | |
dc.date.accessioned | 2012-08-23T14:01:00Z | |
dc.date.available | 2012-08-23T14:01:00Z | |
dc.date.issued | 2002-01-01 | |
dc.identifier.citation | Hop , C E C A , Wang , Y , Kumar , S , Elipe , M V S , Raab , C E , Dean , D C , Poon , G K , Keohane , C-A , Strauss , J , Chiu , S-HL , Curtis , N , Elliott , J , Gerhard , U , Locker , K , Morrison , D , Mortishire-Smith , R , Thomas , S , Watt , A P & Evans , D C 2002 , ' Identification of metabolites of a substance P (Neurokinin 1 receptor) antagonist in rat hepatocytes and rat plasma ' , Drug Metabolism and Disposition , vol. 30 , no. 8 , pp. 937-943 . https://doi.org/10.1124/dmd.30.8.937 | |
dc.identifier.issn | 0090-9556 | |
dc.identifier.other | PURE: 940717 | |
dc.identifier.other | PURE UUID: 2f12db72-06c2-4e6c-9fd6-c1e80020df9f | |
dc.identifier.other | Scopus: 0036320875 | |
dc.identifier.uri | http://hdl.handle.net/2299/8950 | |
dc.description | MEDLINE® is the source for the MeSH terms of this document. | |
dc.description.abstract | [3R,5R,6S]-3-(2-cyclopropyloxy-5-trifluoromethoxyphenyl)-6-phenyl-1-oxa-7 -azaspiro[4.5]decane is a substance P (Neurokinin 1 receptor) antagonist. Substance P antagonists are proven in concept to have excellent potential for the treatment of major depression, and they allow superior and sustained protection from acute and delayed chemotherapy-induced emesis. The metabolism of this compound was investigated in rat hepatocytes, and circulating rat plasma metabolites were identified following oral and intravenous dosing. The turnover in rat hepatocytes within 4 h was about 30%, and the major metabolites were identified as two nitrones and a lactam associated with the piperidine ring. Although these metabolites were also observed in rat plasma, the major circulating metabolite was a keto acid following oxidative de-amination of the piperidine ring. Liquid chromatography/tandem mass spectrometry and nuclear magnetic resonance were used to confirm the structure of the latter metabolite. A mechanism leading to the formation of the keto acid metabolite has been suggested, and most intermediates were observed in rat plasma. | en |
dc.format.extent | 7 | |
dc.language.iso | eng | |
dc.relation.ispartof | Drug Metabolism and Disposition | |
dc.title | Identification of metabolites of a substance P (Neurokinin 1 receptor) antagonist in rat hepatocytes and rat plasma | en |
dc.contributor.institution | Department of Pharmacy | |
dc.contributor.institution | Health & Human Sciences Research Institute | |
dc.description.status | Peer reviewed | |
dc.identifier.url | http://www.scopus.com/inward/record.url?scp=0036320875&partnerID=8YFLogxK | |
rioxxterms.versionofrecord | https://doi.org/10.1124/dmd.30.8.937 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true |
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