Biological activity of platelet activating factor-amidophosphonate (PAF-AP), a novel phosphonolipid selective inhibitor of platelet activating factor (PAF).

A novel amidophosphonate analog of Platelet Activating Factor (PAF), trimethyl (3-phosphonopropyl) ammonium hydroxide (R)-mono[2-acetamido-3-(hexadecyloxy)propyl] ester (PAF-AP), was synthesized. A potent inhibitor of aggregation induced by Platelet Activating Factor, arachidonic acid, Ca2+-ionophore, ADP, and thrombin, PAF-AP had no or very little effect on aggregation induced by epinephrine and collagen. Inhibition of phospholipase A2 and C2 activity was suggested from suppression of release of [14C]-arachidonic acid from pre-labeled platelet glycerophospholipids.