Antiinflammatory and antiarthritic properties of a substituted quinoline carboxylic acid: CL 306,293.
CL 306,293, a substituted quinoline carboxylic acid at a daily oral dose between 1.5 and 3.0 mg/kg suppressed the inflammation and joint destruction (radiological criteria) associated with both developing and established adjuvant arthritis. When a weekly oral dosing regimen was used, joint destruction was attenuated when this agent was administered at a dose of 50 to 200 mg/kg. Inflammation associated with a delayed type hypersensitivity reaction in dogs was suppressed at a daily dose of 0.25 mg/kg or a weekly dose of 1 mg/kg. At efficacious doses, CL 306,293 had no effects on cyclooxygenase or lipoxygenase activities nor did it have an effect on carrageenin induced paw edema. In acute tests, the compound was not ulcerogenic. The above observations indicate that the antiinflammatory effects of CL 306,293 are distinct from those observed with nonsteroidal antiinflammatory agents. Mechanistic studies conducted and to be published indicate that CL 306,293 down regulates T cell function and this mechanism may account, at least in part, for the antiinflammatory and antiarthritic properties observed in animal models of inflammation and joint destruction.
Sloboda
A E
AE
Department of Inflammation, American Cyanamid Company, Lederle Laboratories, Pearl River, NY 10965.
Powell
D
D
Poletto
J F
JF
Pickett
W C
WC
Gibbons
J J
JJ
Bell
D H
DH
Oronsky
A L
AL
Kerwar
S S
SS
D000284:Administration, Oral; D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000473:pathology; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000187:drug effects
D000634:Aminoquinolines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; C071309:3-amino-2-(1,1'-biphenyl)-4-yl-6-fluoro-4-quinolinecarboxylic acid