Nagao T, Ito M, Nagamatsu T, Suzuki Y
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Eur J Pharmacol. 1994 Jul 11;259(3):233-42. doi: 10.1016/0014-2999(94)90649-1.
The antinephritic effect of DP-1904 [6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride], a thromboxane A2 synthetase inhibitor, was compared with that of OKY-046, using an experimental model of nephritis, crescentic-type anti-glomerular basement membrane nephritis. Test drugs were given p.o. once daily from the day after the the development of glomerular alteration as well as the elevation of proteinuria and plasma cholesterol. On the other hand, OKY-046 (20 mg/kg per day), a thromboxane A2 synthetase inhibitor, significantly inhibited only deterioration in the glomeruli. DP-1904 and OKY-046 inhibited glomerular thromboxane B2 production and increased glomerular prostaglandin E2 and 6-keto prostaglandin F1 alpha production in normal and nephritic rats. Both drugs inhibited the increase in platelet aggregability, restored decreased renal tissue blood flow to a near-normal level and decreased the deposition of rat immunoglobulin G on glomerular basement membrane in nephritic rats. These results suggest that DP-1904 may be an effective agent for the treatment of proliferative glomerulonephritis.
使用新月体型抗肾小球基底膜肾炎这一肾炎实验模型，将血栓素A2合成酶抑制剂DP - 1904[6 - (1 - 咪唑基甲基)-5,6,7,8 - 四氢萘 - 2 - 羧酸盐酸盐]的抗肾炎作用与OKY - 046的抗肾炎作用进行了比较。从肾小球病变以及蛋白尿和血浆胆固醇升高后的次日起，每天口服给予受试药物一次。另一方面，血栓素A2合成酶抑制剂OKY - 046(每天20mg/kg)仅显著抑制了肾小球的恶化。DP - 1904和OKY - 046在正常大鼠和肾炎大鼠中均抑制了肾小球血栓素B2的产生，并增加了肾小球前列腺素E2和6 - 酮前列腺素F1α的产生。两种药物均抑制了血小板聚集性的增加，使降低的肾组织血流量恢复到接近正常水平，并减少了肾炎大鼠肾小球基底膜上大鼠免疫球蛋白G的沉积。这些结果表明，DP - 1904可能是治疗增殖性肾小球肾炎的有效药物。
