Antagonistic activity of etizolam on platelet-activating factor. In vivo exeperiments.

Abstract

The ability of etizolam, 6-(o-chlorophenyl)-8-ethyl-1-methyl-4H-s-triazolo[3,4-c]thieno[2,3-e][1,4]diazepine (Y-7131), an anti-anxiety drug, to inhibit platelet-activating factor (PAF)-induced reactions was investigated in experiment animals in vivo. Etizolam (0.01-0.3 mg/kg, i.v.) dose dependently inhibited PAF (0.3 .mu.g/kg, i.v.)-induced bronchoconstriction (Konzett and Rossler''s method) in guinea pigs, but even at doses as large as 3 m/kg, i.v., it has no effect on bronchoconstriction induced by histamine, serotonin, acetylcholine, arachidonic acid, bradykinin, angioten I or leukotriene D4. Etizolam (0.1-1 mg/kg, i.v.) also dose-dependently reversed PAF (1 .mu.g/kg, i.v.)-induced hypotension in anesthetized rats. Injection of PAF into the tail veins of mice produced lethal shock within 10-30 min. Etizolam (0.1-3 mg/kg, i.v. and 1-10 mg/kg, p.o.) protected against the lethal effect of PAF (75 .mu.g/kg, i.v.) in a dose-dependent manner. These results indicate that etizolam specifically inhibits the action of PAF in vivo.