A selective inhibitor of thromboxane synthetase activity of rabbit heart tissue: a pyridazinic derivative.
The effects of 2-(2 dimethylaminoethyl) 5-benzylidene 6-methyl (2H,4H)-3-pyridazinone (III) were studied on the biosynthesis of TXA2 and PGI2 in vitro the TXA2 and PGI2 synthetase activity of heart tissue. Biosyntheses of TXA2 and PGI2 were carried out using arachidonic acid as a substrate and horse platelet and aorta microsomes as sources of TXA2 and PGI2 synthetases respectively. TXB2 and 6-keto PGF1 alpha were determined by RIA. III--did not significantly modify either the biosynthesis of PGI2 in vitro or the PGI2 synthetase activity of heart tissue. did not significantly inhibit TXA2 biosynthesis in vitro but markedly reduced the TXA2 synthetase activity of heart tissue: for a microsomal fraction concentration of 100 micrograms protein, the ID50 was 6.37 X 10(-5) M +/- 1.29 X 10(-8) M. Thus III behaves as a specific inhibitor of the TXA2 synthetase activity of heart tissue and could have a beneficial use in therapeutics.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001593:Benzyl Compounds / Q000494:pharmacology*; D001792:Blood Platelets / Q000648:ultrastructure; D011464:Epoprostenol / Q000096:biosynthesis; D008861:Microsomes / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology*; D011724:Pyridazines / Q000494:pharmacology*; D011817:Rabbits; D011863:Radioimmunoassay; D013928:Thromboxane A2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D001095:Arachidonic Acids; D001593:Benzyl Compounds; D011724:Pyridazines; C057465:2-(2-dimethylaminoethyl)-5-benzylidene-6-methyl-3-pyridazinone; D016718:Arachidonic Acid; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase