title: A review of possible mechanisms of action of the antirheumatic drug, alclofenac.
abstract: A number and variety of hypotheses have been proposed to explain the primary mechanism of action of the antirheumatic drugs. A critical review is made of the biochemical and pharmacological parameters which, on current evidence, parallel the clinical activity of the drugs. The numerous chemical mediators of the inflammatory response are discussed, as is the possible role of endoenous anti-inflammatory substances. Particular attention is paid to the plasma protein-binding effects of antirheumatic drugs and the competitive displacement theory of drug action is examined in the light of recent work on the behaviour of L-tryptophan binding in vitro and in vivo. It is suggested that antirheumatic drugs can be differentiated by their influence on the acute-phase protein response and their effects on tryptophan binding. Clinical findings are reviewed to support the proposal that drugs such as alcofenac, which both inhibit the acute-phase response and exert prolonged influence on the binding of tryptophan to plasma proteins, reduce inflammatory activity more profoundly than those drugs which produce symptomatic relief alone. They are capable, therefore, of altering the course of the disease.
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy; D001667:Binding, Competitive; D001798:Blood Proteins / Q000032:analysis; D002395:Catecholamines / Q000502:physiology; D005768:Gastrointestinal Hormones / Q000502:physiology; D006632:Histamine / Q000502:physiology; D006801:Humans; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010648:Phenylacetates / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D011485:Protein Binding; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects; D012701:Serotonin / Q000502:physiology; D012709:Serum Albumin / Q000032:analysis; D012756:Sheep; D013438:Sulfhydryl Compounds / Q000097:blood; D009626:Terminology as Topic; D014364:Tryptophan / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D001798:Blood Proteins; D002395:Catecholamines; D005768:Gastrointestinal Hormones; D010648:Phenylacetates; D011453:Prostaglandins; D011955:Receptors, Drug; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D012701:Serotonin; D006632:Histamine; D014364:Tryptophan