PAF antagonism as an approach to the treatment of airway hyperreactivity. 1991

C J Meade, and H Heuer
Department of Pharmacology, Boehringer Ingelheim KG, Ingelheim/Rhein, Germany.

Platelet-activating factor (PAF) would seem a good candidate for a mediator of airway hyperreactivity. It has been reported to induce a long-lasting, if modest, increase in hyperreactivity in both experimental animals and humans. Evidence (albeit often indirect) suggests increased levels associated with bronchial hyperreactivity or the related "late-phase reaction" of asthma. In experimental animals, specific inhibitors of PAF can suppress both allergen and PAF-induced hyperreactivity as well as the late-phase reaction to allergen. The mechanism by which PAF induces hyperreactivity is unknown, but the potent effects of PAF on the eosinophil, a cell characteristic of the inflammatory processes often associated with asthma and hyperreactivity, may be important. A number of potent and selective PAF antagonists are now available. The crucial test for the hypothesis that PAF has a role in human airway hyperreactivity will be the testing of substances such as these in appropriate double-blind, placebo-controlled clinical trials.

UI MeSH Term Description Entries
D007783 Lactones Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES. Lactone
D010972 Platelet Activating Factor A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION. AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D004224 Diterpenes Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate. Diterpene,Diterpenes, Cembrane,Diterpenes, Labdane,Diterpenoid,Labdane Diterpene,Norditerpene,Norditerpenes,Norditerpenoid,Cembranes,Diterpenoids,Labdanes,Norditerpenoids,Cembrane Diterpenes,Diterpene, Labdane,Labdane Diterpenes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000485 Allergens Antigen-type substances that produce immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE). Allergen
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001249 Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). Asthma, Bronchial,Bronchial Asthma,Asthmas
D001381 Azepines Seven membered heterocyclic rings containing a NITROGEN atom. Hexamethyleneimines
D014230 Triazoles Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3. Triazole
D016084 Bronchoconstriction Narrowing of the caliber of the BRONCHI, physiologically or as a result of pharmacological intervention. Bronchial Constriction,Bronchial Constrictions,Bronchoconstrictions,Constriction, Bronchial,Constrictions, Bronchial

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