Enhanced prostacyclin biosynthesis and decreased thromboxane formation by 3-dimethylamino 5-(2′,6′-dichlorobenzylidene) 6-methyl (4h)-pyridazine (PC 89).

Abstract

The effects of 3-dimethylamino 5-(2′,6′-dichlorobenzylidene) 6-methyl (4H)-pyridazine (PC 89) on the biosynthesis of PG 12 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 −6M−1.10 −3M)dose-dependently • - enhanced the biosynthesis of PG 12: the AD50 was 6.8×10 −6 M ± 1.2×10 −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 = 3.31×10 −3M ± 4.8×10 −7 M) : this inhibiting actionwas 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.