@article{ref1,
title="The effect of the cytochrome P-450 suicide inactivator, 1-aminobenzotriazole, on the in vivo metabolism and pharmacologic activity of flurazepam",
journal="Drug metabolism and disposition",
year="1990",
author="Capello, S. and Henderson, L. and DeGrazia, F. and Liberato, D. and Garland, W. and Town, C.",
volume="18",
number="2",
pages="190-196",
abstract="Flurazepam (F) is an extensively prescribed hypnotic (Dalmane) whose in vivo activity has been suggested to be due to its primary metabolites, hydroxyethyl flurazepam (HEF) and N-desalkylflurazepam (DAF). In order to determine the intrinsic pharmacologic activity of F, mice were administered various doses of the cytochrome P-450 suicide inactivator, 1-aminobenzotriazole (ABT), 1 hr before the ip administration of 1 mg/kg 14C-F. One hr after 14C-F, 70 mg/kg pentylenetetrazole was administered iv and the mice were observed for convulsions. F alone offered no protection from convulsion (mean brain concentrations were 3.9, 32, and 11 ng/g for F, DAF, and HEF, respectively). F with 25 mg/kg ABT also offered no protection despite a 6-fold increase in brain concentrations of F. F with 100 mg/kg ABT offered a 57% protection from convulsions (mean brain concentrations were 99, 62, and 41 ng/g for F, DAF, and HEF, respectively). One mg/kg F with 400 mg/kg ABT offered 100% protection from convulsions (brain concentrations were 190, 47, and 18 ng/g for F, DAF, and HEF, respectively). These data indicate that F has intrinsic pharmacologic activity which must be considered when evaluating the pharmacodynamics of F.<p /><p>Language: en</p>",
language="en",
issn="0090-9556",
doi="",
url="http://dx.doi.org/"
}