title: Effect of antirheumatic drugs on neutral protease from human leucocyte granules.
abstract: The inhibitory effect of 38 antirheumatic and other agents on purified neutral protease from human polymorphonuclear leucocytes has been studied by determining the decrease in enzyme activity on Z-Ala-NPH as substrate. Analgesics, salicylates, cytostatic agents and steroids, as well as D-penicillamine, colchicine, allopurinol, chlorzoxazone and chlorpromazine, either had no effect on neutral protease or inhibited it only to a very small extent. Typical antirheumatic agents like gold and pyrazolone derivatives suppressed the activity of the enzyme at a concentration of 10(-5)M. The two sulphonated polysaccharides Arteparon and pentosan polysulphate (SP 54) were the most potent inhibitors of neutral protease (inhibition down to 10(-8)M). Increasing concentrations of various inorganic salts gradually suppressed the effect of some otherwise effective drugs on neutral protease. The drugs were completely ineffective at a salt concentration of 0.5 M. At physiological concentrations, however, this effect was insignificant. Inhibition of neutral protease may be one way in which some antirheumatic drugs exert a therapeutic effect in rheumatic diseases.
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D005938:Glucocorticoids / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000494:pharmacology; D006801:Humans; D009504:Neutrophils / Q000201:enzymology*; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology; D011480:Protease Inhibitors; D012965:Sodium Chloride
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D006025:Glycosaminoglycans; D011480:Protease Inhibitors; D010426:Pentosan Sulfuric Polyester; D012965:Sodium Chloride