FORMATION OF A HIGHLY STABLE COMPLEX BETWEEN 5]THIENO[3,2-F]TRIAZOLO-1,2,4[4,3-A]DIAZEPINE-1,4] AND THE PLATELET-ACTIVATING-FACTOR RECEPTORIN RABBIT PLATELET MEMBRANES

BN 50730 [tetrahydro-4,7,8,10 methyl-l(chloro-2 phenyl)-6 (methoxy di phenyl-carbamoyl)-9 pyrido [4',3'-4,5] thieno [3,2-f] triazoio-1,2,4 [ 4,3-alpha] diazepine-1,dr], a novel platelet-activating factor (PAF) r eceptor antagonist with a hetrazepine structure, decreased the maximal number of binding sites (B-max) of [H-3]PAF in rabbit platelet membra nes without altering its dissociation constant. Platelet aggregation i nduced by 1 mu M PAF was prevented by preincubation with 1 mu M BN 507 30. The washing of the platelets preincubated with BN 50730 failed to revert its inhibitory effects. We conclude that BN 50730 acts as a non -competitive antagonist of the PAF receptor, due to the formation of a highly stable drug-receptor complex.