Evaluation of analgesic and anti-inflammatory activity of novel beta-lactam monocyclic compounds

We have examined the in vivo anti-inflammatory and analgesic activity of a new series of monocyclic beta-lactams (azetidinones), similar to others whi ch have been demonstrated to be inhibitors of human leukocyte elastase (HLE ), an enzyme involved in degradation processes of connective tissue. Our ne w compounds have been administered orally (15 mg/kg) to albino rats 30 min before injecting carrageenin in the plantar aponeurosis. Tested compounds h ave demonstrated a certain activity and stability to gastric hydrolysis, in particular two of them markedly reduced paw edema formation, even if sligh tly less effectively than indomethacin (reference compound, 5 mg/kg), To ev aluate the analgesic activity we carried nut the acetic acid writhing test, pretreating rats orally with our compounds 30 min before injecting the aci d solution i.p. The same two molecules which shelved the anti-inflammatory activity demonstrated a very light analgesic activity. These results sugges t the possibility of carrying out further studies, particularly in vitro, o n the mechanism of action of our compounds, mechanism which could be the HL E inhibition.