Biological and pharmacological effects of pinusolide, a novel platelet activating factor antagonist.

Pinusolide, a potent platelet activating factor (PAF) receptor binding antagonist, inhibited PAF-induced aggregation of rabbit platelets with an IC50 value of 5 microM, whereas no inhibitory effects on the aggregation induced by ADP, thrombin, and collagen were observed. Pinusolide protected the mice from PAF-induced lethality with ED50 values of 1.1 mg/kg, i.v. and 69 mg/kg, p.o. Topically given pinusolide at 2 mg/ear effectively inhibited croton oil induced mouse ear edema. All the pinusolide treated ears recovered to normal healthy appearance in a sharp contrast to totally necrotized untreated ears. These results indicated that pinusolide is a potent and specific PAF antagonist in all experimental models as shown in vitro, in vivo, and in animal tests.