Non-steroidal anti-inflammatory drugs if combined with anti-histamine and anti-serotonin agents interfere with the bronchial and platelet effects of "platelet-activating factor" (PAF-acether).
The non-steroidal anti-inflammatory drugs (NSAID) indomethacin, aspirin and salicylic acid, as well as the anti-histamine, mepyramine, and the anti-serotonin, methysergide, fail to interfere with bronchoconstriction, thrombo-cytopenia and hypotension induced by platelet-activating factor (PAF-acether, 1-O-octadecyl-2-acetyl-sn-3-glycerylphosphorylcholine) in the guinea-pig. When one of the NSAID was given combined with mepyramine and with methysergide, bronchoconstriction was suppressed, but thrombocytopenia and hypotension persisted. Platelets prepared from blood collected from animals treated with the NSAID or with mepyramine and/or methysergide, aggregated to a similar extent to PAF-acether; however, the accompanying release of ATP was inhibited in those animals which had been treated with the drug combination effective in vivo against bronchoconstriction. In vitro application to platelets of the drugs effective in vivo and ex vivo was ineffective in blocking the platelet-release reaction. This suggests the existence of in vivo sites of action for the synergistic inhibitory activity of NSAID and anti-histamine/anti-serotonin drugs on bronchoconstriction and on platelet secretion. PAF-acether possible releases from the platelets a bronchoconstrictor component, distinguishable from thromboxane A2 and depleted by reserpine administration to the animals, which could account for the in vivo effects on the bronchopulmonary system.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D001980:Bronchi / Q000187:drug effects*; D004347:Drug Interactions; D006633:Histamine Antagonists / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011738:Pyrilamine / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D006633:Histamine Antagonists; D010972:Platelet Activating Factor; D012702:Serotonin Antagonists; D000255:Adenosine Triphosphate; D011738:Pyrilamine; D008784:Methysergide