Sohda Kin-ya, Minematsu Tsuyoshi, Hashimoto Tadashi, Suzumura Ken-ichi, Funatsu Masashi, Suzuki Katsuhiro, Imai Harumitsu, Usui Takashi, Kamimura Hidetaka
Drug Metabolism Laboratories, Drug Development Division, Yamanouchi Pharmaceutical Co. Ltd., 1-1-8 Azusawa, Itabashi-ku, Tokyo 174-8511, Japan.
Chem Pharm Bull (Tokyo). 2004 Nov;52(11):1322-5. doi: 10.1248/cpb.52.1322.
Zonampanel monohydrate (YM872) has a potent and selective antagonistic effect on the glutamate receptor subtype, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor. Metabolic fingerprinting in rat urine after a single intravenous administration of (14)C-labeled YM872 ((14)C-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.
一水合唑尼沙胺（YM872）对谷氨酸受体亚型α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体具有强效且选择性的拮抗作用。单次静脉注射[¹⁴C]标记的YM872（[¹⁴C]-YM872）后，对大鼠尿液进行代谢指纹图谱分析，发现存在两种代谢物R1和R2。单次静脉注射未标记的YM872后，通过制备型高效液相色谱法从大鼠尿液中对这两种代谢物进行半纯化，并通过包括液相色谱-核磁共振在内的各种仪器分析确定其结构。结果表明，R1和R2分别在喹喔啉二酮骨架的C-7位具有一个羟基氨基和一个氨基。因此，推测YM872在大鼠体内的代谢途径包括硝基还原为羟基氨基，随后再还原为氨基。
