Potentiation of clobazam's anticonvulsant activity by etifoxine, a non-benzodiazepine tranquilizer, in mice. Comparison studies with sodium valproate.
The interaction of two tranquilizers, the 1,5-benzodiazepine clobazam (CBZ, Frisium) and the non-benzodiazepine etifoxin (Hoe-36,801) hydrochloride (EFX, 6-chloro-2-ethylamino-4-methyl-4-phenyl-4H-3,1-benzoxazine HCl) was investigated for anticonvulsant activity in mice. Corresponding experiments were performed with the antiepileptic drug sodium valproate (VPA). Tonic-clonic (maximal) seizures were induced by maximal electroshock (MES; 12 mA, 200 ms) and clonic (threshold) seizures by pentetrazol (PTZ; 85 mg/kg s.c.). The addition of an anticonvulsant threshold dose of EFX (50 mg/kg p.o.) led to an increase of CBZ's potency against both MES- and PTZ-seizures by 410 or 450%, respectively. Under the same conditions, EFX enhanced the potency of VPA only by 20 or 80% and a threshold dose of VPA (100 mg/kg p.o.) enhanced the potency of CBZ by 110 or 0%, respectively. It is concluded that this potentiation of CBZ's anticonvulsant activity by EFX may be beneficially used in epileptic patients either to increase CBZ's antiepileptic effects or to reduce CBZ's therapeutic doses in order to prevent or delay the development of resistance.
D000818:Animals; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000494:pharmacology*; D000078306:Clobazam; D004357:Drug Synergism; D008297:Male; D051379:Mice; D010078:Oxazines / Q000494:pharmacology*; D012640:Seizures / Q000517:prevention & control; D014635:Valproic Acid / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001570:Benzodiazepinones; D010078:Oxazines; D001569:Benzodiazepines; D000078306:Clobazam; D014635:Valproic Acid; C002125:etifoxine