Antirheumatic agents and leukocyte recruitment. New light on the mechanism of action of oxaceprol.
Most anti-inflammatory agents used in the treatment of joint diseases exert inhibitory effects on leukocyte infiltration. Methotrexate, a disease-modifying drug, and corticosteroids also inhibit leukocyte accumulation during inflammation. However, the mechanisms of action of these different compounds on leukocytes vary and in the case of non-steroidal anti-inflammatory drugs (NSAIDs) the mechanism(s) may be indirect. No current drug for inflammatory or degenerative joint disease has been proposed to act specifically by an inhibitory action on neutrophilic leukocytes. Oxaceprol is an amino acid derivative that has been used for several years for the treatment of osteoarthritis and rheumatoid arthritis, ameliorating pain and stiffness and showing good gastrointestinal safety, particularly in comparison with NSAIDs. Recent experimental studies have shown that oxaceprol does not inhibit the synthesis of prostaglandins in vitro, but markedly inhibits neutrophil infiltration into the joints of rats with adjuvant arthritis. These results support earlier screening data showing inhibition by oxaceprol of leukocyte infiltration into sites of acute inflammation. In studies on surgical ischemia reperfusion in hamsters in vivo, oxaceprol was an effective inhibitor of leukocyte adhesion and extravasation. It is proposed that oxaceprol represents a therapeutic agent for degenerative and inflammatory joint diseases, which acts predominantly by inhibiting leukocyte adhesion and migration.
Parnham
M J
MJ
Pharmacological Institute for the Life Sciences, J.W. Goethe University, Frankfurt am Main, Germany. michael.parnham@pliva.hr
D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D002986:Clinical Trials as Topic; D006801:Humans; D006909:Hydroxyproline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007592:Joint Diseases / Q000188:drug therapy* / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; C012393:oxaceprol; D006909:Hydroxyproline