The enantiomers of etodolac, a racemic anti-inflammatory agent, play different roles in efficacy and gastrointestinal safety.

Abstract

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.

• Authors: Naoki Inoue, Masaki Nogawa, Sunao Ito, Koyuki Tajima, Sato Kume, Takashi Kyoi
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 34 Issue 5 Pg. 655-9 ( 2011) ISSN: 1347-5215 [Electronic] Japan
• PMID: 21532152 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Etodolac

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (adverse effects, chemistry, pharmacology)
• Etodolac (adverse effects, chemistry, pharmacology)
• Gastrointestinal Tract (drug effects)
• Male
• Mice
• Rats
• Stereoisomerism