Inhibition of 20 µM etomidate-activated currents by representative benzodiazepines and benzodiazepine-like compounds in the presence of flumazenil. The benzodiazepine:flumazenil concentration ratio was 1:2. (A) 1,7-Me, estazolam, midazolam, and diazepam concentration–response curves for inhibition of etomidate-activated peak current amplitudes. Each data point represents the mean ± SD derived from five different oocytes. The curves are fits of the datasets to a Hill equation yielding 1,7-Me, estazolam, midazolam, and diazepam IC50s of 24 µM (95% CI, 18 to 32 µM), 59 µM (95% CI, 47 to 74 µM), 560 µM (95% CI, 220 to 1400 µM), and 15 µM (95% CI, 11 to 20 µM) respectively. (B) Relationship between the LogIC50 values of the nineteen compounds studied for whom this value could be quantified and their calculated log octanol:water partition coefficient values. A linear fit of this relationship yielded a slope of −0.31 (95% CI, −0.75 to 0.13), which was not significantly different from zero (P = 0.157), and an r2 of 0.114. Error bars indicate the 95% CI. Some symbols overlap.
