The Enantiomers of Etodolac, a Racemic Anti-inflammatory Agent, Play Different Roles in Efficacy and Gastrointestinal Safety
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- Inoue Naoki
- Pharmacology Department, Discovery Research Laboratories, Nippon Shinyaku Co., Ltd.
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- Nogawa Masaki
- Pharmacology Department, Discovery Research Laboratories, Nippon Shinyaku Co., Ltd.
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- Ito Sunao
- Pharmacology Department, Discovery Research Laboratories, Nippon Shinyaku Co., Ltd.
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- Tajima Koyuki
- Pharmacology Department, Discovery Research Laboratories, Nippon Shinyaku Co., Ltd.
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- Kume Sato
- Pharmacology Department, Discovery Research Laboratories, Nippon Shinyaku Co., Ltd.
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- Kyoi Takashi
- Pharmacology Department, Discovery Research Laboratories, Nippon Shinyaku Co., Ltd.
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抄録
The anti-inflammatory agent etodolac is used worldwide and it has a good gastrointestinal safety profile. Etodolac consists of two enantiomers, S- and R-etodolac. Here, we investigated the beneficial activities of racemic etodolac and its enantiomers. First, we compared S- and R-etodolac in terms of their inhibition of cyclooxygenase (COX) activity in vitro and their suppression of paw swelling in adjuvant-induced arthritic rats. The COX-2 inhibitory and anti-inflammatory effects of etodolac were found to be due to the S-enantiomer. We previously reported that etodolac attenuates allodynia in a mouse model of neuropathic pain by a COX-2-independent mechanism [N. Inoue et al., J. Pharmacol. Sci., 109, 600—605 (2009)]. In the present study, we showed that the anti-allodynic effects of etodolac in mice were also due to the S-enantiomer. In addition, we investigated the ulcerogenic activity of racemic etodolac and its enantiomers. At high doses, racemic etodolac showed a lower gastric lesion index in rats than the equivalent dose of S-etodolac. In contrast, R-etodolac showed no ulcerogenic activity and even showed protection against HCl/ethanol-induced gastric damage in rats. In conclusion, S-etodolac exhibited anti-inflammatory effects mediated by COX-2 inhibition and anti-allodynic effects that were independent of COX-2 inhibition, while R-etodolac showed gastroprotective effects that may contribute to the low gastrointestinal toxicity of racemic etodolac. Our results show that each enantiomer plays a different role in the efficacy and gastrointestinal safety of etodolac.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 34 (5), 655-659, 2011
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204625158272
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- NII論文ID
- 130000657775
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC3MvnsFWqug%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 11057852
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- PubMed
- 21532152
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可