Central Effects of Three Fluorinated Benzodiazepines in Comparison with Diazepam

Abstract

The central effects of the 5-(o-fluorophenyl)-3-hydroxybenzodiazepines SAS 643, SAS 646 and Ro 7–5205 were investigated and compared with those of diazepam. It was found that, in rats, these drugs have a pharmacological profile very close to that of diazepam. They possessed a high antimetrazol activity, a muscle-relaxant effect and a depressive action upon exploratory behavior. Moreover, they facilitated behavior suppressed by punishment and caused a synchronization of the EEG pattern. With regard to the relative potencies of the compounds, SAS 646 was found to be the most potent drug by far; it was 4–10 times more potent than diazepam, while SAS 643 was equipotent to the latter. This suggests the usefulness of the new compounds for clinical use. The structure-activity relationships indicate that the general rules stated by Stembach et al are valid also for the group of the 5-(O-fluorophenyl)-3-hydroxybenzodiazepines.

Anticonvulsant Properties of 1,4-Benzodiazepine Derivatives in Amygdaloid-Kindled Seizures and Their Chemical Structure-Related Anticonvulsant Action

“…The same finding was reported by Babbini et al [16] in an anti-pentetrazol test, where introduction of a longer side chain to position 1 reduced the potency. Babbini et al [16] also demonstrated that there was no remarkable difference between a hydrogen group and methyl group at position 1 for anti-pentetrazol activity.…”

“…The same finding was reported by Babbini et al [16] in an anti-pentetrazol test, where introduction of a longer side chain to position 1 reduced the potency. Babbini et al [16] also demonstrated that there was no remarkable difference between a hydrogen group and methyl group at position 1 for anti-pentetrazol activity. However, in the present amygdaloid-kindled seizures, the compounds having a hydrogen group at position 1 had a more potent effect than the compounds with a methyl group at the same position (lorazepam vs. lormetazepam; nitrazepam vs. nimetazepam).…”

BEHAVIOURAL AND PHARMACOKINETIC STUDIES IN THE MONKEY (Macaca mulatta) WITH DIAZEPAM, NORDIAZEPAM AND RELATED 1,4‐BENZODIAZEPINES

“…Though the effect of the parent compounds, diazepam and clorazepate, are uncertain because of the activity of their common metabolite, nordiazepam, the activity (Randall, Scheckel & Pool, 1970;Marcucci, Mussini, Guaitani, Famelli & Garattini, 1971;De Angelis, Traversa & Vertua, 1974;Babbini, Torielli, Gaiardi, Bartoletti & De Marchi, 1974;Babbini, Gaiardi, Bartoletti, Torielli & De Marchi, 1975 …”

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

“…The method has been already described elsewhere (4). Four doses of each drug were tested using 4 -7 animals per dose level.…”