Effect of antirheumatic drugs on neutral protease from human leucocyte granules.

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.