RP 54745, a potential antirheumatic compound. II. In vivo properties in different animal models.
The results obtained with RP 54745, an amino-dithiole-one compound, on stimulated macrophages, revealing inhibition of the hexose monophosphate pathway (HMP), of the exocytosis of lysosomal enzymes and of the production of interleukin-1 (IL-1), by the compound in vitro as well as in vivo, suggested that RP 5475 might influence cells and cytokines implicated in the regulation of the immune system, the disfunctioning of which can lead to inflammatory disorders or autoimmune pathologies. RP 54745 was effective at moderate oral doses (around 5 mg kg-1) in different mouse models of induced arthritis and in the MRL/lpr mice, genetically predisposed to develop an autoimmune pathology including arthritic disorders. The clinical status of the MRL mice, and several of their disturbed biochemical and immunological parameters, improved after a 3-month treatment with RP 54745. This activity of RP 54745 makes it a very attractive antirheumatic compound and a potentially effective treatment in pathologies where IL-1 production is exacerbated.
Folliard
F
F
Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France.
Bousseau
A
A
Terlain
B
B
D000682:Amyloid / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy*; D001799:Blood Sedimentation; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D007546:Isoquinolines / Q000627:therapeutic use*; D008088:Listeriosis / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D012710:Serum Albumin, Bovine; D015054:Zymosan
D000682:Amyloid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007546:Isoquinolines; C077452:RP 54745; D012710:Serum Albumin, Bovine; D015054:Zymosan; D005966:Glucuronidase