ANXIOLYTIC VERSUS SEDATIVE PROPERTIES IN THE BENZODIAZEPINES SERIES - DIFFERENCES IN STRUCTURE-ACTIVITY-RELATIONSHIPS

The effects of three benzodiazepines (Ro 5-3448, Ro 5-3367 and Ro 5-3438) upon conflict behavior and motor activity were investigated. In addition data related to nine other compounds (already published elsewere) were considered in order to study the relationships between anxiolytic and sedative properties in the benzodiazepine series. As regard conflict behavior, Ro 5-3448, Ro 5-3367 and Ro 5-3438 attenuated, in a dose related manner, the suppression of behavior during the punished schedule and, beyond certain doses, they also depressed responding in the nonpunished schedule. Motor activity was constantly depressed by suitable doses of the three drugs. Analysis of variance of data related to all the twelve benzodiazepines showed that the optimal requirements for antianxiety and sedative effects are quite different; furthermore a correlation coefficient of 0.40 between punished and nonpunished behaviors and of 0.88 between nonpunished behavior and motor activity was found, taking in account only the eight very potent alogenated compounds. It was concluded that, in benzodiazepine series, the similarity of effects upon learned and unlearned behaviors is not complete and, more important, that a substantial separation between anxiolytic and sedative activities can be obtained. © 1979.