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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 which have been demonstrated to be inhibitors of human leukocyte elastase (HLE), an enzyme involved in degradation processes of connective tissue. Our new compounds have been administered orally (15 mg/kg) to albino rats 30 min before injecting carrageenin in the plantar aponeurosis. Tested compounds have demonstrated a certain activity and stability to gastric hydrolysis, in particular two of them markedly reduced paw edema formation, even if slightly less effectively than indomethacin (reference compound, 5 mg/kg). To evaluate the analgesic activity we carried out the acetic acid writhing test, pretreating rats orally with our compounds 30 min before injecting the acid solution i.p. The same two molecules which showed the anti-inflammatory activity demonstrated a very light analgesic activity. These results suggest the possibility of carrying out further studies, particularly in vitro, on the mechanism of action of our compounds, mechanism which could be the HLE inhibition.