Enhanced prostacyclin biosynthesis and decreased thromboxane formation by 3-dimethylamino 5-(2',6'-dichlorobenzylidene) 6-methyl (4H)-pyridazine (PC 89).
The effects of 3-dimethylamino 5-(2',6'-dichlorobenzylidene) 6-methyl (4H)-pyridazine (PC 89) on the biosynthesis of PG I2 and TX A2 using horse aorta and horse platelet microsomes as sources of enzymes and arachidonic acid as substrate, were investigated. PC 89 (1.10(-6) M- 1.10(-3) M) dose-dependently - enhanced the biosynthesis of PG I2: the AD50 was 6.8 X 10(-6) M +/- 1.2 X 10(-9) M, the Vmax did not vary significantly with concentrations: PC 89 increased the affinity of enzyme for substrate - but inhibited TX A2 biosynthesis (ID50 = 3.31 X 10(-3) M +/- 4.8 X 10(-7) M): this inhibiting action was not of competitive type. Owing to this dual activity of preventing TX A2 formation and stimulating PG I2 biosynthesis, PC 89 could be a valuable drug for myocardial ischemia and atherosclerosis therapeutics.
D000818:Animals; D001011:Aorta / Q000378:metabolism; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D003327:Coronary Disease / Q000188:drug therapy; D011464:Epoprostenol / Q000096:biosynthesis*; D006736:Horses; D066298:In Vitro Techniques; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D001095:Arachidonic Acids; D011724:Pyridazines; D013931:Thromboxanes; D016718:Arachidonic Acid; D013928:Thromboxane A2; C046377:3-dimethylamino-5-(2',6'-dichlorobenzylidene)-6-methyl(4H)-pyridazine; D011464:Epoprostenol