Formation of a highly stable complex between BN 50730 [tetrahydro-4,7,8,10 methyl-1(chloro-2 phenyl)-6 (methoxy-4 phenyl-carbamoyl)-9 pyrido [4',3'-4,5] thieno [3,2-f] triazolo-1,2,4 [4,3-a] diazepine-1,4] and the platelet-activating factor receptor in rabbit platelet membranes

BN 50730 [tetrahydro-4,7,8,10 methyl-1(chloro-2 phenyl)-6 (methoxy-4 phenyl-carbamoyl)-9 pyrido [4',3'-4,5] thieno [3,2-f] triazolo-1,2,4 [4,3-alpha] diazepine-1,4], a novel platelet-activating factor (PAF) receptor antagonist with a hetrazepine structure, decreased the maximal number of binding sites (Bmax) of [3H]PAF in rabbit platelet membranes without altering its dissociation constant. Platelet aggregation induced by 1 microM PAF was prevented by preincubation with 1 microM BN 50730. 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.