Comparative in vitro studies of the metabolism of six 4-substituted methamphetamines and their inhibition of cytochrome P450 2D6 by GC-MS with trifluoroacetyl derivatization.

• Material Type: 博士論文
• Title: Comparative in vitro studies of the metabolism of six 4-substituted methamphetamines and their inhibition of cytochrome P450 2D6 by GC-MS with trifluoroacetyl derivatization.
• Volume: 4 4
• Author/Editor: TANIGUCHI, Masashi
• Author Heading: TANIGUCHI, Masashi
• Publication, Distribution, etc.: Scientific Research
• Publication Date: 2013-04
• Publication Date (W3CDTF): 2013-04
• Periodical title: American Journal of Analytical Chemistry
• Degree grantor/type: 滋賀医科大学
• Date Granted: 2013-09-11
• Date Granted (W3CDTF): 2013-09-11
• Dissertation Number: 乙第395号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 乙第395号
• Text Language Code: eng
• Subject Heading: Methamphetamine; Designer Drug; GC-MS; TFA Derivatization; Interaction; Metabolism
• Target Audience: 一般
• Note (General): Use of new amphetamine-type stimulants (ATS) as designer drugs is a serious problem worldwide. ATS are used in tablet, capsule, and powder forms, and can be mixed with other drugs. There is little information available on how these new drugs are metabolized or their ability to inhibit the metabolism of co-administered drugs. This study aimed to investigate the metabolism of six 4-substituted analogs of methamphetamine (MA), and their potential inhibition of MA metabolism. The metabolism of MA and the 4-substituted MAs was examined in vitro using human metabolic enzymes. Metabolite analyses were performed using trifluoroacetyl derivatization and GC-MS. The experiments showed that cytochrome P450 2D6 (CYP2D6) was involved in the major metabolic pathway of MA, where it catalyzed N-demethylation of 4-fluoromethamphetamine (4-FMA), 4-chloromethamphetamine (4-CMA), 4-bromomethamphetamine (4-BMA), 4-iodomethamphetamine (4-IMA) and 4-nitromethamphetamine (4-NMA), and O-demethylation of 4-methoxymethamphetamine (4-MMA). The half maximal inhibitory concentration (IC50) values for CYP2D6 using MA as substrate were different for each of the 4-substituted MAs. The strongest inhibitors of amphetamine production from MA were, in order, 4-IMA, 4-BMA, 4-CMA, 4-MMA, 4-FMA, and 4-NMA. The same order was observed for the IC50 values for inhibition of p-hydroxymethamphetamine production from MA, except for the IC50 of 4-MMA. The IC50 values of 4-IMA were lower than the IC50 values of fluoxetine and higher than that of quinidine. The results of this study imply that the risk of illicit drug interactions fluctuates so widely that unintentional fatal drug poisonings could occur.; Thesis or Dissertation; 学位論文題目 : Study on forensic drug testing of methamphetamines and related compounds by GC-MS with trifluoroacetyl derivatization.; 平成25年度; 10.4236/ajac.2013.44022
• DOI: info:doi/10.4236/ajac.2013.44022; https://doi.org/info:doi/10.4236/ajac.2013.44022
• Persistent ID (NDL): info:ndljp/pid/8948691; https://dl.ndl.go.jp/pid/8948691
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Available (W3CDTF): 2015-03-03
• Date Accepted (W3CDTF): 2015-02-03T05:25:05+09:00
• Date Created (W3CDTF): 2017-02-17
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10422/4200; https://shiga-med.repo.nii.ac.jp/records/1293
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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