The effects of hetrazepine PAF antagonists in preclinical models of asthma.

In different disease related animal models of asthma selective and potent hetrazepine paf-antagonists (like the hetrazepines WEB 2086 and WEB 2170) inhibit (i) allergen-induced bronchoconstriction, (ii) antigen-induced infiltrations of eosinophils, (iii) lung-edema formation by antigen, (iv) late phase response and (v) bronchial hyperreactivity to antigen. In addition the formation and release of other mediators (like leukotrienes, thromboxanes, histamine) are inhibited in vivo, although a direct interaction of hetrazepinoic paf-antagonists with these mediators has been excluded. The participation of paf in a chain of pathophysiological events involving other mediators, and the possibility of synergistic interactions, open up the possibility that antagonists of paf may have apparent effects extending beyond those anticipated for a single mediator.