Comparative study in mice of ten 1,4-benzodiazepines and of clobazam: anticonvulsant, anxiolytic, sedative, and myorelaxant effects.
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 predictive 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.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000927:Anticonvulsants / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology*; D000078306:Clobazam; D004827:Epilepsy / Q000188:drug therapy; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001570:Benzodiazepinones; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D000078306:Clobazam