Effects of a new 1,3,4‐thiadiazolium mesoionic compound, MI‐D, on the acute inflammatory response

A new mesoionic compound, 4‐phenyl‐5‐(4‐nitro‐cinnamoyl)‐1,3,4‐thiadiazolium‐2‐phenylamine (MI‐D), is described along with some of its biological properties. Its effects on hepatic metabolism, on O   2 −and nitric oxide (NO) production, and in in vivo models for potential antinociceptive, antipyretic, and antiinflammatory activities were determined. In perfused rat liver, MI‐D (25 µM) stimulated glycogenolysis (95%), and inhibited oxygen uptake (37%) with affecting glycolysis. In phorbol 12‐myristate 13‐acetate‐stimulated macrophages, O   2 −generation was reduced (95%) by MI‐D (15 µM), whereas the production of NO was unaffected. MI‐D (2 mg/kg) inhibited (55%) the number of abdominal writhings induced by acetic acid. At 1 mg/kg, MI‐D inhibited the febrile response (5 h) induced by lipopolysaccharide (LPS) and was also effective against a preexisting febrile response. Treatment with MI‐D (1 mg/kg) reduced by 67% prostaglandin (PGE 2 ) levels in the cerebrospinal fluid of LPS‐exposed mice, and at a higher dose (8 mg/kg) MI‐D inhibited paw edema formation (2 h) induced by carrageenan. MI‐D has a spectrum of activities similar to other nonsteroidal antiinflammatory drugs, qualifying it as a potential anti‐inflammatory drug. Drug Dev. Res. 61:207–217, 2004. © 2004 Wiley‐Liss, Inc.