Effects of a novel PAF antagonist, E6123, on PAF-induced biological responses.
E6123 is a new member of the benzodiazepine class of PAF antagonists. Although it has similar activity in vitro to the two representative antagonists WEB2347 and Y24180, in vivo it is far more active than these compounds. Thus E6123 was effective in inhibiting dose-dependently PAF-induced bronchoconstriction when administered orally or intravenously (IC50 1.0 and 1.3 micrograms/Kg, respectively, at 3 hr), and had a minimum effective dose of 10 micrograms/Kg and 3 micrograms/Kg, respectively, against PAF-induced hematoconcentration and edema at 3 hr after oral administration. Furthermore, E6123 protects mice from PAF-induced death dose-dependently (ED50 7 micrograms/Kg at 3 hr). In conclusion, E6123 should prove valuable in pharmacological and clinical research into the roles of PAF, and in therapy of diseases such as asthma, in which PAF is assumed to play a pathological role.
Tsunoda
H
H
Tsukuba Research Lab., Eisai Co., Ltd., Ibaraki, Japan.
Sakuma
Y
Y
Harada
K
K
Muramoto
K
K
Katayama
S
S
Horie
T
T
Shimomura
N
N
Clark
R
R
Miyazawa
S
S
Okano
K
K
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D016085:Bronchoconstrictor Agents; D010972:Platelet Activating Factor; D014230:Triazoles; C068034:WEB 2347; C068035:4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-6,9-dimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine; C068033:E 6123