[Effects of PAF antagonists in experimental models. Therapeutical perspectives]

Abstract

The discovery, during the last ten years, of Platelet Activating Factor (PAF) antagonists with different frameworks, but efficient on platelets tests, led the authors to study their activity in vivo against PAF-induced effects. These antagonists inhibit, with various potencies, the effects of PAF administration such as hypotension and bronchoconstriction in different animal species. Since PAF is assumed to play a central role in many diseases, effects of its antagonists have been studied in experimentally induced pathologies and in few clinical studies. We have been particularly interested in their effects on the first manifestation of asthma which is hypersensitivity. This manifestation is experimentally reproduced by anaphylactic bronchoconstriction, usually in the guinea-pig. Our results showed that different sensitization procedures may determine the relative efficiency of a PAF antagonist on subsequent antigen challenge. Indeed, the booster injection of antigen to a pre-sensitized animal could account for the refractoriness of anaphylactic bronchoconstriction to PAF antagonists. This booster injection mimics the clinical situation of atopic patients repeatedly exposed to allergen. Thus, it seems that immediate hypersensitivity could not be treated by the unique administration of a PAF antagonist. However, those antagonists may have more benefit in the clinical management of the late phase of asthma and of hyperreactivity and could thus provide anti-asthmatic drugs. PAF antagonists may have also therapeutical effects in septic shock, in myocardial ischemia and cardiac rhythm disturbances, in brain damage following cerebral ischemia and neurological trauma, in gastric and intestinal damages or in some inflammatory reactions.