Effects of 2-indolecarbohydrazides on thromboxane synthetase activity and on in vitro and ex vivo blood platelet aggregation. New selective inhibitors.
Platelet antiaggregatory action of 42 synthetic 2-indolecarbohydrazides was studied observing their actions on arachidonic acid (AA) and adenosine-5-diphosphate (ADP) induced platelet aggregation. Radioimmunoassay studies, following AA induced aggregation, measuring thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were carried out on those compounds whose previous activities included inhibition of AA induced platelet aggregation and inhibition of the second wave of aggregation using ADP as the aggregating agent. Those compounds which demonstrated inhibition of TXB2 with increased PGE2 were subsequently tested with PGH2 as the aggregating agent. Results of this work demonstrate that 3 of the 42 compounds have specific inhibitory activity for thromboxane synthetase. The most active compounds were 1-methyl-5-hydroxyindole derivatives.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D015232:Dinoprostone; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D044262:Prostaglandin H2; D011458:Prostaglandins E / Q000096:biosynthesis; D011463:Prostaglandins H / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000378:metabolism*
D001095:Arachidonic Acids; D006834:Hydrazines; D007211:Indoles; D011450:Prostaglandin Endoperoxides, Synthetic; D011458:Prostaglandins E; D011463:Prostaglandins H; D016718:Arachidonic Acid; D044262:Prostaglandin H2; D013930:Thromboxane-A Synthase; D015232:Dinoprostone