Platelet-activating factor antagonists.

Over the past decade platelet-activating factor has achieved the status of an important inflammatory mediator. The scientific enthusiasm and number of research investigators, publications, and meetings recently devoted to PAF suggest that this mediator will be the subject of continued study in the foreseeable future. The potential for the presence and involvement of PAF in human disease is easily concluded from the reports described in this review. Both the need for low concentrations for cellular response and the rapid biological clearance mechanisms have made the proof of the involvement of PAF in human disease difficult. The discovery of PAF receptor antagonists and structure-activity relationships of such antagonists (159) will make this determination possible in the near future. The current PAF antagonists may be considered as first generation agents, since the most potent antagonist is still less than 1/100th as potent as PAF is as an agonist. The wide diversity of clinical applications from asthma to septic shock may also require antagonists with selective attributes such as delivery route (oral vs intravenous vs topical) or biological half-life (prolonged vs short). PAF may prove to be the key mediator of several poorly understood disease syndromes such as hyperacute organ transplant rejection, ischemic bowel necrosis (160), and adult respiratory distress syndrome. We must wait for clinical results to draw further conclusions.