Abstract
Recent research on asthma mediators has concentrated more and more on platelet-activating factor (PAF), which is one of the most potent bronchoconstrictors known thus far. Inhalant PAF challenge in healthy volunteers may provide a mean of testing PAF antagonists. The usefulness of the PAF provocation test in measuring the pharmacologic activity of a new PAF antagonist, WEB-2086, has been examined in 12 healthy volunteers in a double-blind, placebo-controlled, within-subject crossover study. PAF-induced immediate bronchoconstriction, slight hemodynamic changes, and PAF-related subjective side effects. Premedication with WEB-2086 (40 mg) completely prevented any increase in airway resistance after PAF inhalation, as well as development of most of the cardiovascular and side effects induced by PAF. The clear protection against PAF-induced pharmacologic effects can be explained by the specific PAF-antagonistic activity of WEB-2086. The method described in this article may be applied as a useful tool for looking at PAF-antagonistic activity in healthy volunteers.
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