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.
Lefort
J
J
Unité associée Institut Pasteur/INSERM U 285, Département de Physiopathologie expérimentale, Paris, France.
Sedivy
P
P
Desquand
S
S
Randon
J
J
Coëffier
E
E
Maridonneau-Parini
I
I
Floch
A
A
Benveniste
J
J
Vargaftig
B B
BB
D000818:Animals; D001772:Blood Cell Count; D001792:Blood Platelets / Q000187:drug effects; D001993:Bronchodilator Agents; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010477:Perfusion; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D011863:Radioimmunoassay; D013481:Superoxides / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood
D001993:Bronchodilator Agents; D010972:Platelet Activating Factor; D011725:Pyridines; D013844:Thiazoles; D013481:Superoxides; D013929:Thromboxane B2; D009240:N-Formylmethionine Leucyl-Phenylalanine; C052520:3-(3-pyridinyl)-1H,3H-pyrrolo(1,2-c)thiazole-7-carboxamide