PAF-乙酰醚拮抗剂48740 R.P.的药理学特性

Pharmacological profile of 48740 R.P., a PAF-acether antagonist.

作者信息

Lefort J, Sedivy P, Desquand S, Randon J, Coëffier E, Maridonneau-Parini I, Floch A, Benveniste J, Vargaftig B B

机构信息

Unité associée Institut Pasteur/INSERM U 285, Département de Physiopathologie expérimentale, Paris, France.

出版信息

Eur J Pharmacol. 1988 Jun 10;150(3):257-68. doi: 10.1016/0014-2999(88)90006-4.

DOI:10.1016/0014-2999(88)90006-4

PMID:2843382

Abstract

The pyrrolo-thiazole derivative 48740 R.P. inhibited the platelet-activating factor (PAF-acether)-induced aggregation of human and rabbit platelets and was poorly effective against ADP- and arachidonic acid-induced platelet aggregation. 48740 R.P. prevented the activation of guinea-pig alveolar macrophages by PAF-acether, and the PAF-acether-induced thromboxane B2 production from guinea-pig lungs. 48740 R.P. (3 mg/kg i.v.) antagonized selectively in anaesthetized guinea-pigs the bronchoconstriction due to PAF-acether without affecting that due to acetylcholine, histamine, serotonin, thromboxane A2 analogue U-46,619 and arachidonic acid. A higher dose of 48740 R.P. (10 mg/kg i.v.) was required to block the thrombocytopenia and the leucopenia induced by PAF-acether in the propranolol-treated guinea-pigs. 48740 R.P. (30 mg/kg i.v.) antagonized the PAF-acether effects when bronchoconstriction was induced by aerosolized PAF-acether. 48740 R.P. is a selective antagonist of PAF-acether under in vitro and in vivo conditions.

摘要

吡咯并噻唑衍生物48740 R.P.抑制血小板活化因子（PAF - 乙酰醚）诱导的人及兔血小板聚集，而对ADP和花生四烯酸诱导的血小板聚集作用较弱。48740 R.P.可阻止PAF - 乙酰醚对豚鼠肺泡巨噬细胞的激活，以及PAF - 乙酰醚诱导的豚鼠肺组织血栓素B2的产生。48740 R.P.（静脉注射3 mg/kg）在麻醉豚鼠中可选择性拮抗PAF - 乙酰醚引起的支气管收缩，而不影响乙酰胆碱、组胺、5 - 羟色胺、血栓素A2类似物U - 46,619和花生四烯酸引起的支气管收缩。在普萘洛尔处理的豚鼠中，需要更高剂量的48740 R.P.（静脉注射10 mg/kg）才能阻断PAF - 乙酰醚诱导的血小板减少和白细胞减少。当雾化PAF - 乙酰醚诱导支气管收缩时，48740 R.P.（静脉注射30 mg/kg）可拮抗PAF - 乙酰醚的作用。48740 R.P.在体外和体内条件下均为PAF - 乙酰醚的选择性拮抗剂。