EFFECT OF DP-1904, A THROMBOXANE A(2) SYNTHETASE INHIBITOR, ON CRESCENTIC NEPHRITIS IN RATS

The antinephritic effect of DP-1904 methyl)-5,6,7,8-tetrahydronaphthal ene-2-carboxylic acid hydrochloride], a thromboxane A(2) synthetase in hibitor, was compared with that of OKY-046, using an experimental mode l of nephritis, crescentic-type anti-glomerular basement membrane neph ritis. Test drugs were given p.o. once daily from the day after the an ti-glomerular basement membrane serum injection to the 40th day. DP-19 04 (5, 15 and 45 mg/kg per day) markedly inhibited the development of glomerular alteration as well as the elevation of proteinuria and plas ma cholesterol. On the other hand, OKY-046 (20 mg/kg per day), a throm boxane A(2) synthetase inhibitor, significantly inhibited only deterio ration in the glomeruli. DP-1904 and OKY-046 inhibited glomerular thro mboxane B-2 production and increased glomerular prostaglandin E(2) and 6-keto prostaglandin F-1 alpha production in normal and nephritic rat s. Both drugs inhibited the increase in platelet aggregability, restor ed decreased renal tissue blood flow to a near-normal level and decrea sed the deposition of rat immunoglobulin G on glomerular basement memb rane in nephritic rats. These results suggest that DP-1904 may be an e ffective agent for the treatment of proliferative glomerulonephritis.