Anti-inflammatory,Analgesic and Ulcerogenic Properties of S-(+)-Ibuproxam,Racemic Ibuproxam-β-cyclodextrin and S-(+)-Ibuproxam-β-cyclodextrin

The anti-inflammatory, analgesic and gastric mucosal damage-inducing activities of S-(+)-ibuproxam, and S-(+)-ibuproxam-β-cyclodextrin, new propionic acid derivatives, and racemic ibuproxam-β-cyclodextrin were investigated in three animal models and compared with those of racemic ibuproxam, racemic ibuprofen and its optical enantiomer S-(+)-ibuprofen. The anti-inflammatory activities of racemic ibuprofen, S-(+)-ibuprofen and racemic ibuproxam in carrageenan-induced paw oedema in rats were almost equipotent and slightly greater than those of S-(+)-ibuproxam and S-(+)-ibuproxam-β-cyclodextrin, and significantly greater than that of racemic ibuproxam-β-cyclodextrin. In abdominal constriction tests in mice, the analgesic effects of racemic ibuproxam, S-(+)-ibuproxam, racemic ibuproxam-β-cyclodextrin and S-(+)-ibuproxam-β-cyclodextrin were significantly less pronounced than those of racemic ibuprofen and S-(+)-ibuprofen. Ulcerogenic activity of S-(+)-ibuproxam-β-cyclodextrin in rats was found to be significantly weaker than that of racemic ibuproxam-β-cyclodextrin, racemic ibuproxam and S-(+)-ibuproxam and, most notably, weaker than those of racemic ibuprofen ans S-(+)ibuprofen. These results indicate that S-(+)-ibuproxam-β-cyclodextrin could be a novel potent anti-inflammatory and analgesic agent with a therapeutic index more favourable than that of the classical non-steroid anti-inflammatory drugs ibuprofen and ibuproxam.