Pharmacological profile of epiyangambin: a furofuran lignan with PAF antagonist activity.
The ability of a furofuran lignan, epiyangambin, to inhibit PAF-induced rabbit platelet aggregation in vitro and thrombocytopenia in rats was investigated. Epiyangambin dose-dependently inhibited PAF-induced platelet aggregation without modifying the amplitude of the maximal response, indicating a competitive antagonism. The IC50 value of epiyangambin for 10(-9) M PAF-induced aggregation was 6.1 x 10(-7) M and the Schild analysis provided a pA2 of 6.91 +/- 0.2 with a slope of 0.98 +/- 0.25 (n = 4) and a pKb of 6.94 +/- 0.19. Epiyangambin had no effect upon the platelet aggregation induced by collagen, thrombin or ADP. The in vivo administration of the lignan at 20 mg/kg significantly inhibited PAF-induced thrombocytopenia in rats. These data indicate that epiyangambin is a potent and selective antagonist of PAF both in vitro and in vivo.
Castro-Faria-Neto
H C
HC
Departamento de Fisiologia e Farmacodinâmica, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Martins
M A
MA
Silva
P M
PM
Bozza
P T
PT
Cruz
H N
HN
de Queiroz-Paulo
M
M
Kaplan
M A
MA
Cordeiro
R S
RS
D000818:Animals; D005663:Furans / Q000494:pharmacology*; D017705:Lignans; D008031:Lignin / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*
D005663:Furans; D017705:Lignans; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; C082827:epiyangambin; D008031:Lignin