Pharmacological profile of G619, a new platelet aggregation inhibitor.

Abstract:

:G619, a 4-OH-isophthalic acid derivative, was studied for its capacity to inhibit platelet aggregation. G619 dose-dependently inhibited U46619, collagen, ADP, PAF, thrombin and epinephrine-induced platelet aggregation in vitro. The IC50 values for inhibition of U46619-induced human and rabbit platelet aggregation were 39 and 43 microM, respectively. G619, at 100 microM, inhibited high concentration collagen (10 micrograms/ml)-induced aggregation of rabbit platelets pretreated with indomethacin and increased the level of cAMP in washed rabbit platelets by 30% (p less than 0.01 vs basal). However, G619, did not inhibit fibrinogen binding to GPIIb/IIIa receptor, phosphodiesterase, U46619-induced contractile responses on canine saphenous vein or rabbit aorta, calcium-induced vasoconstriction and thrombin or PAF-induced elevation of [Ca++]i in platelets in vitro. In vivo, the U46619-induced maximal thrombocytopenia in rats was reduced from 40% (vehicle) to 22% and 18% by 10 and 30 mg/kg of G619 i.v., respectively. G619 (30 mg/kg) had no effect on the U46619-induced vasopressor response or sudden death in rats, and had no effect on TxB2 formation. Our results indicate that G619 is a broad-spectrum platelet aggregation inhibitor and may have its effect on a common mechanism for platelet aggregation besides an effect on the thromboxane A2 receptor.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Yue TL,Smith EF 3rd,Ohlstein EH,Sulpizio A,Slivjak MJ,Rabinovici R,Sellers TS,Lynch KM,Poyser R,Feuerstein G

doi

10.1016/0049-3848(92)90283-g

subject

Has Abstract

pub_date

1992-05-15 00:00:00

pages

331-47

issue

4

eissn

0049-3848

issn

1879-2472

journal_volume

66

pub_type

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