title: Metabolic profiling of the Uncaria hook alkaloid geissoschizine methyl ether in rat and human liver microsomes using high-performance liquid chromatography with tandem mass spectrometry.
abstract: Geissoschizine methyl ether (GM) is an indole alkaloid found in Uncaria hook, which is a galenical constituent of yokukansan, a traditional Japanese medicine. GM has been identified as the active component responsible for anti-aggressive effects. In this study, the metabolic profiling of GM in rat and human liver microsomes was investigated. Thirteen metabolites of GM were elucidated and identified using a high-performance liquid chromatography with tandem mass spectrometry method, and their molecular structures were proposed on the basis of the characteristics of their precursor ions, product ions, and chromatographic retention times. There were no differences in the metabolites between the rat and human liver microsomes. Among the 13 identified metabolites, there were two demethylation metabolites, one dehydrogenation metabolite, three methylation metabolites, three oxidation metabolites, two water-adduct metabolites, one di-demethylation metabolite, and one water-adduct metabolite followed by oxidation. The metabolic pathways of GM were proposed on the basis of this study. This study will be helpful in understanding the metabolic routes of GM and related Uncaria hook alkaloids, and provide useful information on the pharmacokinetics and pharmacodynamics. This is the first report that describes the separation and identification of GM metabolites in rat and human liver microsomes.
authors: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. kushida_hirotaka@mail.tsumura.co.jp.
authors: Hirotaka
authors: H
authors: Kushida
authors: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. matsumoto_takashi@mail.tsumura.co.jp.
authors: Takashi
authors: T
authors: Matsumoto
authors: Kampo Formulation Development Center, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. igarashi_yasushi@mail.tsumura.co.jp.
authors: Yasushi
authors: Y
authors: Igarashi
authors: Kampo Formulation Development Center, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. nishimura_hiroaki@mail.tsumura.co.jp.
authors: Hiroaki
authors: H
authors: Nishimura
authors: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. watanabe_junko@mail.tsumura.co.jp.
authors: Junko
authors: J
authors: Watanabe
authors: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. maemura_kazuya@mail.tsumura.co.jp.
authors: Kazuya
authors: K
authors: Maemura
authors: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. kase_yoshio@mail.tsumura.co.jp.
authors: Yoshio
authors: Y
authors: Kase
mesh_terms: D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D006865:Hydrogenation; D026121:Indole Alkaloids / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D014149:Tranquilizing Agents / Q000378:metabolism*; D032070:Uncaria / Q000737:chemistry*
chemical_list: D026121:Indole Alkaloids; D010936:Plant Extracts; D014149:Tranquilizing Agents; C110832:geissoschizine methylether
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