[Pharmacological studies on proglumetacin maleate, a new non-steroidal anti-inflammatory drug. (1). Anti-inflammatory effects].
Anti-inflammatory effects of proglumetacin maleate (PGM), a new indomethacin (IND) derivative, were compared with those of IND on an equimolar-dose basis. PGM produced a dose-dependent inhibition of vascular permeability and carrageenin edema. These inhibitory effects of PGM were greater when given 4 hr prior to phlogistic agents than when given 1 hr before. Moreover, these effects of PGM were long-acting. Inhibitory effects of PGM on kaolin edema and UV-erythema were slightly less active than those of IND. PGM markedly reduced the leukocyte migration in carrageenin pleurisy. Subacute anti-exudative and anti-granuloma effects of PGM were nearly equal to those of IND. Also, PGM showed strong prophylactic and therapeutic effects on adjuvant arthritis, the model of chronic (immuno-reactive) inflammation. These effects of PGM were superior or equal to those of IND. These pharmacological properties of PGM suggested its potential usefulness in rheumatic and other inflammatory disorders. It was considered that the mode of action of PGM mainly depended on its active metabolite, IND. However, PGM was also active in the case of local administration into the sites of inflammation on rat hind paw edema. Therefore, it seemed that PGM had a different behavior than a so called "prodrug".
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001168:Arthritis / Q000188:drug therapy; D002199:Capillary Permeability / Q000187:drug effects; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006168:Guinea Pigs; D007210:Indoleacetic Acids / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007210:Indoleacetic Acids; D002351:Carrageenan; C019541:proglumetacin; D007213:Indomethacin