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.
Yang
H O
HO
Natural Products Research Institute, Seoul National University, Republic of Korea.
Kang
Y H
YH
Suh
D Y
DY
Kim
Y C
YC
Han
B H
BH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; C101973:pinusolide