Influence of N₁-2-Hydroxyethyl Substitution on Central Activity of Oxazepam and Lorazepam

Abstract

The central activities of two N₁-2-hy droxyethyl substituted derivatives of oxazepam and lorazepam (SAS 602 and SAS 632, respectively) were compared with those of the parent compounds. It was found that in rats all the drugs had antimetrazol activity and produced muscle relaxant effects and depressive ac tions upon exploratory behavior. They were all active in facilitating behavior suppressed by punishment, and caused a synchronization of the EEG pattern lasting 4–5 h. Both N₁-2-hydroxyethyl substituted compounds showed a reduced potency when compared with oxazepam and lorazepam. Compound SAS 632, however, was more active than oxazepam in conflict behavior, with less muscle relaxant activity. This could suggest a usefulness of the compound for clinical use.

General Pharmacology and Neuropharmacology of Benzodiazepine Derivatives

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Influence of the 2’-Chloro Substitution on Central Activity of Desmethyldiazepam

“…This would be not in accordance with Greenblatt's statement (13) that hydroxy sub stitution in position 3 reduces the potency of the compound. From the data reported in the literature (18) and from our works (3,5), however, it can be inferred that general rules concerning structure-activity relationships in benzodiazepine series are not absolute, this being especially true when very active com pounds are dealt with. A better understanding of this matter could be achieved by investigat ing homologous series of benzodiazepines of high potency.…”