Comparative effects of azapropazone on cellular events at inflamed sites. Influence on joint pathology in arthritic rats, leucocyte superoxide and eicosanoid production, platelet aggregation, synthesis of cartilage proteoglycans, synovial production and actions of interleukin-1 in cartilage resorption correlated with drug uptake into cartilage in-vitro.
Azapropazone (APZ) has been compared with standard NSAIDs in title systems to establish aspects of its mode of action on cellular events at inflamed sites. APZ (150 mg kg-1 day-1) given for 10-13 days exhibited a reduction in joint pathology in established adjuvant arthritis in rats comparable with that of indomethacin (2 mg kg-1 day-1) and clobuzarit (20 mg kg-1 day-1). APZ was shown to be a potent inhibitor of the production of leucocyte superoxide and synovial interleukin-1 (IL-1)-like activity and stimulated articular cartilage proteoglycan synthesis, but was ineffective as an inhibitor of platelet aggregation or IL-1 induced cartilage degradation in-vitro. These in-vitro effects may have relevance to the mode of action of this weak inhibitor of prostaglandin synthesis.
Rainsford
K D
KD
Anti-inflammatory Research Unit, Strangeways Research Laboratory, Cambridge, UK.
Davies
A
A
Mundy
L
L
Ginsburg
I
I
D000818:Animals; D001032:Apazone / Q000493:pharmacokinetics / Q000494:pharmacology*; D001168:Arthritis / Q000503:physiopathology*; D001169:Arthritis, Experimental / Q000378:metabolism / Q000503:physiopathology*; D002358:Cartilage, Articular / Q000378:metabolism; D002417:Cattle; D005260:Female; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000096:biosynthesis*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides; D013552:Swine; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism; D014227:Triazines / Q000494:pharmacology*
D007375:Interleukin-1; D011453:Prostaglandins; D011509:Proteoglycans; D014227:Triazines; D013481:Superoxides; D001032:Apazone