AU-8001

4-Acetamidophenyl-2-(5'-p-toluyl-1'-methylpyrrole)acetate (AU 8001), a tolmetin derivative, prepared by esterification with paracetamol, showed antiinflammatory-antirheumatic activity in animal models. This activity is believed to be largely due to the ability of the drug to inhibit the synthesis of prostaglandins. Furthermore, there is evidence that AU 8001 may also reduce the leucocyte immigration into inflamed tissues. Moreover, AU 8001 had no effects, after oral administration, on histamine- and 5-hydroxytryptamine-induced increase of vascular permeability or lysosome membrane stabilization.

Antiinflammatory, analgesic, antipyretic and gastrointestinal ulcerogenic activities of 4-acetamidophenyl-2-(5'-p-toluyl-1'-methylpyrrole)acetate (AU 8001), a new nonsteroidal antiinflammatory drug, have been investigated and compared with those of tolmetin at equimolar doses in experimental animals. 1. AU 8001 showed inhibitory action on acute and subacute inflammation such as carrageenin hind paw edema and pellet-induced granuloma formation, with an activity similar to that of tolmetin. However, AU 8001 was more active as an antiarthritic agent than tolmetin. AU 8001 had no topical antiinflammatory effect. 2. The analgesic activities of AU 8001 measured by the writhing test and the Randall-Selitto method were comparable to those of tolmetin. Both compounds were ineffective in the hotplate test. 3. AU 8001 also had antipyretic activity but its potency was inferior to tolmetin and acetylsalicylic acid (ASA). 4. AU 8001 elicited almost negligible side effects in the gastrointestinal tract. The ulcerogenic activity of AU 8001, in particular, was extremely weak in relation to tolmetin, indometacin and ASA. 5. AU 8001 caused no appreciable changes in the general behaviour of animals after oral administration.