Effects of a new antihypertensive agent, SGB-1534, on rat platelet aggregation.
The present study was designed to examine the antiplatelet activity of SGB-1534, 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]ethyl]-2,4(1H, 3H)- quinazolinedione monohydrochloride, compared with prazosin, ketanserin and aspirin. The equihypotensive doses of SGB-1534, prazosin and ketanserin were administered orally to rats; and 1 hr later, their effects on collagen-induced platelet aggregation, compared with those of aspirin, were examined under ex vivo conditions. The bleeding time was determined by using the tail transection method. SGB-1534 (10 mg/kg) as well as ketanserin (3 and 10 mg/kg) and aspirin (10 mg/kg) effectively inhibited the platelet aggregation; and in addition, they significantly prolonged bleeding times. Prazosin in doses of 10 and 30 mg/kg did not affect either the aggregation or bleeding times. Whereas 10(-4) M aspirin significantly inhibited the production of malondialdehyde (MDA) in rat platelets, SGB-1534, prazosin and ketanserin even in considerably high concentrations (10(-4) or 10(-3) M) did not affect the MDA production and the cyclic AMP levels in the platelets. In isolated rat femoral arteries, SGB-1534, prazosin and ketanserin antagonized the contractile response to phenylephrine with pA2 values of approximately 10.06, 10.39 and 7.71, respectively. Also, SGB-1534 and ketanserin attenuated the contractile response to 5-hydroxytryptamine (5-HT) with pA2 values of 6.36 and 9.53, respectively, while prazosin had no antagonistic effects on 5-HT-induced contraction.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D011799:Quinazolines; D012701:Serotonin; D008315:Malondialdehyde; C042712:SGB 1534; D000242:Cyclic AMP