文章基本信息

标题：The Enantiomers of Etodolac, a Racemic Anti-inflammatory Agent, Play Different Roles in Efficacy and Gastrointestinal Safety
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作者：Naoki Inoue ; Masaki Nogawa ; Sunao Ito 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2011
卷号：34
期号：5
页码：655-659
DOI：10.1248/bpb.34.655
出版社：The Pharmaceutical Society of Japan
摘要：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.
关键词：etodolac;enantiomer;adjuvant arthritis;neuropathic pain;ulcerogenic activity