Comparative study in mice of tetrazepam and other centrally active skeletal muscle relaxants.
Tetrazepam is a 1,4 benzodiazepine (BZD) clinically used in France and Germany as a muscle relaxant. The activity of tetrazepam was compared to that of diazepam, baclofen, mephenesin and chlormezanone in mice, in pharmacological models which are predictive of muscle relaxant and sedative properties. Tetrazepam was active in all the 6 tests of muscle relaxation (traction, chimney, inclined screen, grip force, horizontal grid and morphine-induced Straub tail). The overall muscle relaxant potency of tetrazepam was inferior to that of diazepam, but was clearly superior to that of chlormezanone and mephenesin. Baclofen was less active than tetrazepam in 3 tests (traction, horizontal grid, and grip strength), but more active in the other 3 tests. The administration of the benzodiazepine receptor antagonist Ro 15-1788 blocked the effects of tetrazepam and diazepam in 2 representative tests, morphine-induced Straub tail and the rotarod test, but did not modify the activities of the other centrally acting muscle relaxants in these same models. The selectivity ratio (ED50 rotarod or ED50 locomotor activity/ED50 in each muscle relaxant test) for tetrazepam was superior to that of diazepam and all the other muscle relaxant drugs examined. It is concluded that tetrazepam exerts its muscle relaxant activity by stimulating central BZD receptors, and presents the advantage of a wide dissociation between muscle relaxant and sedative potencies.
Simiand
J
J
Sanofi Recherche, Toulouse, France.
Keane
P E
PE
Biziere
K
K
Soubrie
P
P
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001418:Baclofen / Q000494:pharmacology; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000494:pharmacology*; D002720:Chlormezanone / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D008615:Mephenesin / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D009125:Muscle Relaxants, Central; D001569:Benzodiazepines; D005442:Flumazenil; D009020:Morphine; D008615:Mephenesin; C005245:tetrazepam; D002720:Chlormezanone; D001418:Baclofen; D003975:Diazepam