Effect of a prostaglandin E1 derivative (OP-1206) and acetylsalicylic acid on electrically induced thrombosis in guinea-pig mesenteric artery and its modification by an inhibitor of prostaglandin I2 synthetase, tranylcypromine.
The antithrombotic effect of a prostaglandin E1 derivative, OP-1206 (17S-20-dimethyl-trans-delta 2-PGE1) X alpha-cyclodextrin clathrate (OP-1206 X alpha-CD), was compared with that of acetylsalicylic acid (ASA) in a electrically induced thrombosis model of guinea-pig mesenteric arteries using intact animals and animals subjected to the superfusion of tranylcypromine (TC, 15 mM) over their mesentery. The drug-effect was assessed by the change of the threshold voltage for the thrombus formation. 1) TC (1.5-15 mM) lowered the threshold voltage, and the effect was comparable to its inhibitory effect on PGI2 formation in vitro, suggesting that PGI2 generated in mesenteric arteries acts to prevent thrombus formation. 2) In intact animals, OP-1206 X alpha-CD at doses of 0.01-0.3 mg/kg, p.o. (as OP-1206), significantly and dose-dependently elevated the threshold voltage. ASA (30-1000 mg/kg, p.o.) significantly elevated the threshold voltage, but the effect reached to its maximum at 100 mg/kg and lessened with further increase of ASA. 3) In TC-treated animals, OP-1206 X alpha-CD elevated the threshold voltage dose-dependently, but the elevation of threshold voltage by ASA reached to its plateau level which was significantly lower than that obtained with OP-1206 X alpha-CD at 0.3 mg/kg, indicating that the antithrombotic effect of ASA is incomplete in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System; D004347:Drug Interactions; D004558:Electric Stimulation; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005343:Fibrinolytic Agents; D006168:Guinea Pigs; D019746:Intramolecular Oxidoreductases; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D008641:Mesenteric Vascular Occlusion / Q000209:etiology / Q000517:prevention & control*; D014191:Tranylcypromine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D005343:Fibrinolytic Agents; D014665:Vasodilator Agents; D014191:Tranylcypromine; C025090:ONO 1206; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D000527:Alprostadil; D001241:Aspirin