Structure-affinity relationships between several new benzodiazepine derivatives and 3H-diazepam receptor sites.

Publisher Website
Google Scholar
Abstract
Several new benzodiazepines were studied with respect to their ability to bind specifically to benzodiazepine receptor sites in rat cerebral cortex membrane fraction. The IC50 [median inhibitory concentration] values of new benzodiazepines were compared to that of diazepam. A group of triazolo-[1,4] benzodiazepines displaced 3H-diazepam very effectively. The most potent of this group was brotizolam. Its potency was about 10 times higher than that of diazepam. Camazepam, which differs from diazepam in its C-3 substitution, had the lowest affinity to the benzodiazepine receptor site. This potency was about 0.006 that of diazepam. CM 7116 [7-chloro-5-(2-fluorophenyl)-1,3 dihydro-2H-1,4-benzodiazepin-2 one] bound with the highest affinity to the benzodiazepine receptor site among the metabolites of CM 6912 [loflazepate ethyl]. The length of the side chain at the C-3 position of this compound is shorter than that of the other metabolites of CM 6912. The long side chain at the C-3 position may inhibit a close interaction between the receptor site and the substrate molecule, thereby leading to low-affinity binding.

This publication has 3 references indexed in Scilit: