Inhibition of platelet thromboxane synthesis by 7-(1-imidazolyl) heptanoic acid: dissociation from inhibition of aggregation

The effects of 7-(1-imidazolyl)heptanoic acid (7-IHA), a thromboxane synthetase inhibitor, and indomethacin on platelet aggregation and immunoreactive thromboxane B₂ (iTXB₂) synthesis were studied in human platelet rich plasma. The ID₅₀ for inhibition of arachidonic acid induced iTXB₂ synthesis by 7-IHA was 1.9 μM but the ID₅₀ for inhibition of platelet aggregation was estimated to be 1.35 mM. 7-IHA (0.5 mM) inhibited arachidonic acid induced iTXB₂ synthesis to values less than that obtained in the presence of indomethacin (10 μM); but did not inhibit aggregation, while indomethacin completely inhibited platelet aggregation. 7-IHA had no effect on platelet fatty acid cyclooxygenase; did not promote synergism with ADP or arachidonic acid; arachidonic acid plus ADP or stable PGH₂ analogs. We conclude: 1) that 7-IHA is a specific inhibitor of platelet thromboxane synthesis which at the same concentrations does not inhibit arachidonic acid induced platelet aggregation and 2) that inhibition of platelet TXA₂ synthesis by thromboxane synthetase inhibitors may not necessarily inhibit arachidonic acid induced platelet aggregation.