Silva C L, Cruz H N, Violante F A, Cordeiro R S, Martins M A, Noël F
Departamento de Farmacologia Basica e Clínica, Universidade Federal do Rio de Janeiro, Brazil.
Biochem Pharmacol. 1996 Jan 26;51(2):193-6. doi: 10.1016/0006-2952(95)02158-2.
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.
BN 50730 [四氢-4,7,8,10-甲基-1-(氯-2-苯基)-6-(甲氧基-4-苯基氨基甲酰基)-9-吡啶并[4',3'-4,5]噻吩并[3,2-f]三唑并-1,2,4[4,3-α]二氮杂卓-1,4]，一种具有杂氮卓结构的新型血小板活化因子(PAF)受体拮抗剂，可降低兔血小板膜中[3H]PAF的最大结合位点数(Bmax)，而不改变其解离常数。1 microM BN 50730预孵育可阻止1 microM PAF诱导的血小板聚集。用BN 50730预孵育的血小板洗涤后，其抑制作用未能恢复。我们得出结论，由于形成了高度稳定的药物-受体复合物，BN 50730作为PAF受体的非竞争性拮抗剂发挥作用。
