Comparative Study in Mice of Ten 1,4‐Benzodiazepines and of Clobazam: Anticonvulsant, Anxiolytic, Sedative, and Myorelaxant Effects

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Abstract
We will present data from the comparison between four tests in mice of 10 1,4-benzodiazepines and one 1,5-benzodiazepine (clobazam). The tests used were: the "4 plates test" of anxiolytic activity; the electroshock test to determine the anticonvulsive effects; actimetry to predict the sedative effect on motricity; and traction test to predict the myorelaxant effect. The latter two tests have been suggested to be predicitve of side-effects that damage psychomotor efficiency in human patients. A comparison of ED50s determined from the predictive tests of the therapeutic effect and those of the side-effects led to the calculation of ratios considered to be predictive of the safety margin. A classification according to this margin shows the advantages of the 1,5-benzodiazepine compared with the 1,4-benzodiazepines. Despite the caution needed in the extrapolation of the results from animals to humans, this work stresses the interesting place that the 1,5-benzodiazepine seem to hold as anticonvulsant in clinical practice.