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

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.