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 wit h an IC50 value of 5 mu M, whereas no inhibitory effects on the aggreg ation induced by ADP, thrombin, and collagen were observed. Pinusolide protected the mice from PAF-induced lethality with ED(50) 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 sh arp contrast to totally necrotized untreated ears. These results indic ated that pinusolide is a potent and specific PAF antagonist in all ex perimental models as shown in vitro, in vivo, and in animal tests.