Effect of DP-1904, a thromboxane A2 synthetase inhibitor, on crescentic nephritis in rats.
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.
Nagao
T
T
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Ito
M
M
Nagamatsu
T
T
Suzuki
Y
Y
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D015232:Dinoprostone / Q000652:urine; D005455:Fluorescent Antibody Technique; D007093:Imidazoles / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009395:Nephritis, Interstitial / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D010974:Platelet Aggregation / Q000502:physiology; D011507:Proteinuria / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D008689:Methacrylates; D013764:Tetrahydronaphthalenes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D002784:Cholesterol; C056295:nafagrel; D013930:Thromboxane-A Synthase; D015232:Dinoprostone; C034364:ozagrel