Application of LC-NMR for Characterization of Rat Urinary Metabolites of Zonampanel Monohydrate (YM872)
Zonampanel monohydrate (YM872) has a potent and selective antagonistic effect on the glutamate receptor subtype, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor. Metabolic fingerprinting in rat urine after a single intravenous administration of 14C-labeled YM872 (14C-YM872) reve...
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| Veröffentlicht in: | Chemical & Pharmaceutical Bulletin 2004, Vol.52(11), pp.1322-1325 |
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| creator | Sohda, Kin-ya Minematsu, Tsuyoshi Hashimoto, Tadashi Suzumura, Ken-ichi Funatsu, Masashi Suzuki, Katsuhiro Imai, Harumitsu Usui, Takashi Kamimura, Hidetaka |
| description | Zonampanel monohydrate (YM872) has a potent and selective antagonistic effect on the glutamate receptor subtype, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor. Metabolic fingerprinting in rat urine after a single intravenous administration of 14C-labeled YM872 (14C-YM872) revealed the presence of two metabolites, R1 and R2. The two metabolites were semi-purified by preparative HPLC from rat urine after a single intravenous administration of non-labeled YM872, and their structures were elucidated by various instrumental analyses involving LC-NMR. The results showed that R1 and R2 have a hydroxyamino group and an amino group at the C-7 position of the quinoxalinedione skeleton, respectively. Therefore, the proposed metabolic pathway of YM872 in rats involves the reduction of the nitro group to a hydroxyamino group and then subsequent reduction to an amino group. |
| doi_str_mv | 10.1248/cpb.52.1322 |
| format | Article |
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Metabolic fingerprinting in rat urine after a single intravenous administration of 14C-labeled YM872 (14C-YM872) revealed the presence of two metabolites, R1 and R2. The two metabolites were semi-purified by preparative HPLC from rat urine after a single intravenous administration of non-labeled YM872, and their structures were elucidated by various instrumental analyses involving LC-NMR. The results showed that R1 and R2 have a hydroxyamino group and an amino group at the C-7 position of the quinoxalinedione skeleton, respectively. Therefore, the proposed metabolic pathway of YM872 in rats involves the reduction of the nitro group to a hydroxyamino group and then subsequent reduction to an amino group.</description><identifier>ISSN: 0009-2363</identifier><identifier>EISSN: 1347-5223</identifier><identifier>DOI: 10.1248/cpb.52.1322</identifier><identifier>PMID: 15516754</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Animals ; Chromatography, Liquid - methods ; Imidazoles - chemistry ; Imidazoles - metabolism ; Imidazoles - urine ; LC-NMR ; Magnetic Resonance Spectroscopy - methods ; Male ; Quinoxalines - chemistry ; Quinoxalines - metabolism ; Quinoxalines - urine ; Rats ; Rats, Sprague-Dawley ; urinary metabolite ; YM872 ; zonampanel monohydrate ; α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist</subject><ispartof>Chemical and Pharmaceutical Bulletin, 2004, Vol.52(11), pp.1322-1325</ispartof><rights>2004 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-7f5342ff30ea807bc7be0fab727f5d499354bc0f318987eed47600686ea5dfcc3</citedby><cites>FETCH-LOGICAL-c691t-7f5342ff30ea807bc7be0fab727f5d499354bc0f318987eed47600686ea5dfcc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15516754$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sohda, Kin-ya</creatorcontrib><creatorcontrib>Minematsu, Tsuyoshi</creatorcontrib><creatorcontrib>Hashimoto, Tadashi</creatorcontrib><creatorcontrib>Suzumura, Ken-ichi</creatorcontrib><creatorcontrib>Funatsu, Masashi</creatorcontrib><creatorcontrib>Suzuki, Katsuhiro</creatorcontrib><creatorcontrib>Imai, Harumitsu</creatorcontrib><creatorcontrib>Usui, Takashi</creatorcontrib><creatorcontrib>Kamimura, Hidetaka</creatorcontrib><creatorcontrib>bAnalysis Research</creatorcontrib><creatorcontrib>Institute for Drug Discovery Research</creatorcontrib><creatorcontrib>Ltd</creatorcontrib><creatorcontrib>Yamanouchi Pharmaceutical Co</creatorcontrib><creatorcontrib>Analysis & Metabolism Laboratories</creatorcontrib><creatorcontrib>Drug Development Division</creatorcontrib><creatorcontrib>aDrug Metabolism Laboratories</creatorcontrib><title>Application of LC-NMR for Characterization of Rat Urinary Metabolites of Zonampanel Monohydrate (YM872)</title><title>Chemical & Pharmaceutical Bulletin</title><addtitle>Chem. Pharm. Bull.</addtitle><description>Zonampanel monohydrate (YM872) has a potent and selective antagonistic effect on the glutamate receptor subtype, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor. Metabolic fingerprinting in rat urine after a single intravenous administration of 14C-labeled YM872 (14C-YM872) revealed the presence of two metabolites, R1 and R2. The two metabolites were semi-purified by preparative HPLC from rat urine after a single intravenous administration of non-labeled YM872, and their structures were elucidated by various instrumental analyses involving LC-NMR. The results showed that R1 and R2 have a hydroxyamino group and an amino group at the C-7 position of the quinoxalinedione skeleton, respectively. Therefore, the proposed metabolic pathway of YM872 in rats involves the reduction of the nitro group to a hydroxyamino group and then subsequent reduction to an amino group.</description><subject>Animals</subject><subject>Chromatography, Liquid - methods</subject><subject>Imidazoles - chemistry</subject><subject>Imidazoles - metabolism</subject><subject>Imidazoles - urine</subject><subject>LC-NMR</subject><subject>Magnetic Resonance Spectroscopy - methods</subject><subject>Male</subject><subject>Quinoxalines - chemistry</subject><subject>Quinoxalines - metabolism</subject><subject>Quinoxalines - urine</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>urinary metabolite</subject><subject>YM872</subject><subject>zonampanel monohydrate</subject><subject>α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist</subject><issn>0009-2363</issn><issn>1347-5223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc-LEzEcxYMobl09eZcBQRSZ-s3vmeNadBVahcU96CVkMsk2ZToZk_Sw_vVmbOmCh3xzeB_e9-UFoZcYlpiw5oOZuiUnS0wJeYQWmDJZc0LoY7QAgLYmVNAL9CylHQDhIOlTdIE5x0JytkB3V9M0eKOzD2MVXLVe1d82N5ULsVptddQm2-j_nOUbnavb6Ecd76uNzboLg882zdKvMOr9pEc7VJswhu19H3W21dufm0aSd8_RE6eHZF-c7kt0-_nTj9WXev39-uvqal0b0eJcS8cpI85RsLoB2RnZWXC6k6QoPWtbyllnwFHctI20tmdSAIhGWM17Zwy9RG-OvlMMvw82ZbX3ydhhKMHCISkhgTAuSAFf_wfuwiGOJZvCTABtqBC8UO-PlIkhpWidmqLfl9crDGpuX5X2FSdqbr_Qr06eh25v-wf2VHcBro9AUUvpQxgHP9qHzSZJs7V7rwgAUwCcYKygnNl-HhyD5K2cnT4enXYp6zt7XqVj9maw51j4NP8ZnMXys8qO9C9KWKxT</recordid><startdate>20041101</startdate><enddate>20041101</enddate><creator>Sohda, Kin-ya</creator><creator>Minematsu, Tsuyoshi</creator><creator>Hashimoto, Tadashi</creator><creator>Suzumura, Ken-ichi</creator><creator>Funatsu, Masashi</creator><creator>Suzuki, Katsuhiro</creator><creator>Imai, Harumitsu</creator><creator>Usui, Takashi</creator><creator>Kamimura, Hidetaka</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20041101</creationdate><title>Application of LC-NMR for Characterization of Rat Urinary Metabolites of Zonampanel Monohydrate (YM872)</title><author>Sohda, Kin-ya ; Minematsu, Tsuyoshi ; Hashimoto, Tadashi ; Suzumura, Ken-ichi ; Funatsu, Masashi ; Suzuki, Katsuhiro ; Imai, Harumitsu ; Usui, Takashi ; Kamimura, Hidetaka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-7f5342ff30ea807bc7be0fab727f5d499354bc0f318987eed47600686ea5dfcc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Chromatography, Liquid - methods</topic><topic>Imidazoles - chemistry</topic><topic>Imidazoles - metabolism</topic><topic>Imidazoles - urine</topic><topic>LC-NMR</topic><topic>Magnetic Resonance Spectroscopy - methods</topic><topic>Male</topic><topic>Quinoxalines - chemistry</topic><topic>Quinoxalines - metabolism</topic><topic>Quinoxalines - urine</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>urinary metabolite</topic><topic>YM872</topic><topic>zonampanel monohydrate</topic><topic>α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sohda, Kin-ya</creatorcontrib><creatorcontrib>Minematsu, Tsuyoshi</creatorcontrib><creatorcontrib>Hashimoto, Tadashi</creatorcontrib><creatorcontrib>Suzumura, Ken-ichi</creatorcontrib><creatorcontrib>Funatsu, Masashi</creatorcontrib><creatorcontrib>Suzuki, Katsuhiro</creatorcontrib><creatorcontrib>Imai, Harumitsu</creatorcontrib><creatorcontrib>Usui, Takashi</creatorcontrib><creatorcontrib>Kamimura, Hidetaka</creatorcontrib><creatorcontrib>bAnalysis Research</creatorcontrib><creatorcontrib>Institute for Drug Discovery Research</creatorcontrib><creatorcontrib>Ltd</creatorcontrib><creatorcontrib>Yamanouchi Pharmaceutical Co</creatorcontrib><creatorcontrib>Analysis & Metabolism Laboratories</creatorcontrib><creatorcontrib>Drug Development Division</creatorcontrib><creatorcontrib>aDrug Metabolism Laboratories</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Chemical & Pharmaceutical Bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sohda, Kin-ya</au><au>Minematsu, Tsuyoshi</au><au>Hashimoto, Tadashi</au><au>Suzumura, Ken-ichi</au><au>Funatsu, Masashi</au><au>Suzuki, Katsuhiro</au><au>Imai, Harumitsu</au><au>Usui, Takashi</au><au>Kamimura, Hidetaka</au><aucorp>bAnalysis Research</aucorp><aucorp>Institute for Drug Discovery Research</aucorp><aucorp>Ltd</aucorp><aucorp>Yamanouchi Pharmaceutical Co</aucorp><aucorp>Analysis & Metabolism Laboratories</aucorp><aucorp>Drug Development Division</aucorp><aucorp>aDrug Metabolism Laboratories</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Application of LC-NMR for Characterization of Rat Urinary Metabolites of Zonampanel Monohydrate (YM872)</atitle><jtitle>Chemical & Pharmaceutical Bulletin</jtitle><addtitle>Chem. Pharm. Bull.</addtitle><date>2004-11-01</date><risdate>2004</risdate><volume>52</volume><issue>11</issue><spage>1322</spage><epage>1325</epage><pages>1322-1325</pages><issn>0009-2363</issn><eissn>1347-5223</eissn><abstract>Zonampanel monohydrate (YM872) has a potent and selective antagonistic effect on the glutamate receptor subtype, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor. Metabolic fingerprinting in rat urine after a single intravenous administration of 14C-labeled YM872 (14C-YM872) revealed the presence of two metabolites, R1 and R2. The two metabolites were semi-purified by preparative HPLC from rat urine after a single intravenous administration of non-labeled YM872, and their structures were elucidated by various instrumental analyses involving LC-NMR. The results showed that R1 and R2 have a hydroxyamino group and an amino group at the C-7 position of the quinoxalinedione skeleton, respectively. Therefore, the proposed metabolic pathway of YM872 in rats involves the reduction of the nitro group to a hydroxyamino group and then subsequent reduction to an amino group.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>15516754</pmid><doi>10.1248/cpb.52.1322</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Chromatography, Liquid - methods Imidazoles - chemistry Imidazoles - metabolism Imidazoles - urine LC-NMR Magnetic Resonance Spectroscopy - methods Male Quinoxalines - chemistry Quinoxalines - metabolism Quinoxalines - urine Rats Rats, Sprague-Dawley urinary metabolite YM872 zonampanel monohydrate α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist |
| title | Application of LC-NMR for Characterization of Rat Urinary Metabolites of Zonampanel Monohydrate (YM872) |
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