Anti-inflammatory, analgesic and ulcerogenic properties of S-(+)-ibuproxam, racemic ibuproxam-beta-cyclodextrin and S-(+)-ibuproxam-beta-cyclodextrin.
The anti-inflammatory, analgesic and gastric mucosal damage-inducing activities of S-(+)-ibuproxam, and S-(+)-ibuproxam-beta-cyclodextrin, new propionic acid derivatives, and racemic ibuproxam-beta-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-beta-cyclodextrin, and significantly greater than that of racemic ibuproxam-beta-cyclodextrin. In abdominal constriction tests in mice, the analgesic effects of racemic ibuproxam, S-(+)-ibuproxam, racemic ibuproxam-beta-cyclodextrin and S-(+)-ibuproxam-beta-cyclodextrin were significantly less pronounced than those of racemic ibuprofen and S-(+)-ibuprofen. Ulcerogenic activity of S-(+)-ibuproxam-beta-cyclodextrin in rats was found to be significantly weaker than that of racemic ibuproxam-beta-cyclodextrin, racemic ibuproxam and S-(+)-ibuproxam and, most notably, weaker than those of racemic ibuprofen and S-(+)ibuprofen. These results indicate that S-(+)-ibuproxam-beta-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.
Bole-Vunduk
B
B
LEK Pharmaceutical and Chemical Company d.d., Research and Development, Ljubljana, Slovenia.
Verhnjak
K
K
Zmitek
J
J
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology*; D044482:Benzeneacetamides; D003505:Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D007052:Ibuprofen / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D013237:Stereoisomerism; D047392:beta-Cyclodextrins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D044482:Benzeneacetamides; D003505:Cyclodextrins; D004338:Drug Combinations; D006877:Hydroxamic Acids; D047392:beta-Cyclodextrins; C031215:betadex; C025377:ibuproxam; D007052:Ibuprofen