etifoxine has been researched along with Seizures* in 6 studies
6 other study(ies) available for etifoxine and Seizures
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Differential effects of etifoxine on anxiety-like behaviour and convulsions in BALB/cByJ and C57BL/6J mice: any relation to overexpression of central GABAA receptor beta2 subunits?
Dysfunction of GABAergic transmission related to abnormal expression of GABA(A) receptor subunits in specific brain regions underlies some pathological anxiety states. Besides involvement of the benzodiazepine recognition site of GABA(A) receptor in the expression of anxiety-like behaviour, the roles of the β(2)/β(3) subunits are not well characterized. To address this issue, the experimental design of this study utilized the GABAergic compound etifoxine (with a preferential effectiveness after binding to a specific site at β(2)/β(3) subunits) tested in two inbred mouse strains: BALB/cByJ and C57BL/6J mice using three behavioural paradigms (light/dark box, elevated plus maze and restraint stress-induced small intestinal transit inhibition) and the t-butylbicyclophosphorothionate-induced convulsions model. Etifoxine plasma and brain levels and β(2)/β(3) mRNAs and protein expression levels in various brain regions were compared between the two strains. The two mouse strains differed markedly in basal anxiety level. Etifoxine exhibited more pronounced anxiolytic and anticonvulsant effects in the BALB/cByJ mice compared to the C57BL/6J mice. The etifoxine brain/plasma ratios of the two strains were not different. Beta2 subunit mRNA and protein expression levels were around 25 and 10% higher respectively in the anterodorsal nucleus of the thalamus and the CA3 field of hippocampus of BALB/cByJ mice compared to C57BL/6J mice. Beta3 subunit mRNA and protein expression levels did not differ between the two strains. Based on these results, it is suggested that overexpression of GABA(A) receptor β(2) subunit in BALB/cByJ mice relative to C57BL/6j mice contributes to the dysfunction in GABA(A) transmission in regions of brain known to regulate responses to stress. The dysregulated GABA(A) function in BALB/cByJ mice may be corrected by the administration of etifoxine. Topics: Animals; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Behavior, Animal; Brain; Hippocampus; Intestine, Small; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Motor Activity; Oxazines; Receptors, GABA-A; Seizures | 2011 |
The anxiolytic etifoxine protects against convulsant and anxiogenic aspects of the alcohol withdrawal syndrome in mice.
Change in the function of gamma-aminobutyric acid(A) (GABA(A)) receptors attributable to alterations in receptor subunit composition is one of main molecular mechanisms with those affecting the glutamatergic system which accompany prolonged alcohol (ethanol) intake. These changes explain in part the central nervous system hyperexcitability consequently to ethanol administration cessation. Hyperexcitability associated with ethanol withdrawal is expressed by physical signs, such as tremors, convulsions, and heightened anxiety in animal models as well as in humans. The present work investigated the effects of anxiolytic compound etifoxine on ethanol-withdrawal paradigms in a mouse model. The benzodiazepine diazepam was chosen as reference compound. Ethanol was given to NMRI mice by a liquid diet at 3% for 8 days, then at 4% for 7 days. Under these conditions, ethanol blood level ranged between 0.5 and 2 g/L for a daily ethanol intake varying from 24 to 30 g/kg. These parameters permitted the emergence of ethanol-withdrawal symptoms once ethanol administration was terminated. Etifoxine (12.5-25 mg/kg) and diazepam (1-4 mg/kg) injected intraperitoneally 3h 30 min after ethanol removal, decreased the severity in handling-induced tremors and convulsions in the period of 4-6h after withdrawal from chronic ethanol treatment. In addition when administered at 30 and 15 min, respectively, before the light and dark box test, etifoxine (50mg/kg) and diazepam (1mg/kg) inhibited enhanced aversive response 8h after ethanol withdrawal. Etifoxine at 25 and 50 mg/kg doses was without effects on spontaneous locomotor activity and did not exhibit ataxic effects on the rota rod in animals not treated with ethanol. These findings demonstrate that the GABAergic compound etifoxine selectively reduces the physical signs and anxiety-like behavior associated with ethanol withdrawal in a mouse model and may hold promise in the treatment of ethanol-withdrawal syndrome in humans. Topics: Animals; Anti-Anxiety Agents; Anxiety; Diazepam; Ethanol; GABA Agonists; Male; Mice; Models, Animal; Motor Activity; Oxazines; Receptors, GABA-A; Seizures; Substance Withdrawal Syndrome | 2009 |
Investigation of the anticonvulsive effect of acute immobilization stress in anxious Balb/cByJ mice using GABA A-related mechanistic probes.
A disordered regulation of neuroactive steroids release in response to acute stress could induce GABAergic dysfunctions underlying anxiety disorders.. First, we conducted studies indicating that a short immobilization stress in anxious Balb/cByJ mice produced an anticonvulsive effect. Second, the effects of different positive allosteric modulators (etifoxine, progesterone, clonazepam, and allopregnanolone) of GABA A receptors were compared in a mouse model mimicking the disruption of the acute stress-induced neuroactive steroids release with finasteride (types I and II 5alpha-reductase inhibitor).. The acute stress-induced anticonvulsive effect, expressed by the threshold dose of t-butylbicyclophosphorothionate-producing clonic seizures, was time-dependent. The extent of the enhancement of acute stress-induced anticonvulsive effect was lowered in the presence of finasteride. The same effect was observed with PK11195, which behaves as an antagonist of the peripheral benzodiazepine receptor in the dose range used in this study. Picrotoxin reduced the acute stress anticonvulsive effect, proving that this effect operates through the GABA A receptor. Contrary to progesterone (up to 30 mg/kg), etifoxine (50 mg/kg), allopregnanolone (10 mg/kg), and clonazepam (10 microg/kg) inhibited the finasteride effect in stressed animals. The effect of etifoxine was blocked in the presence of finasteride and picrotoxin combined in stressed animals.. These findings support the hypothesis suggesting an involvement of neuroactive steroids in the anticonvulsive effect of restraint stress. The dual and complementary mechanisms of action of etifoxine (directly on the GABA A receptor and indirectly via the neuroactive steroids) may represent a therapeutic benefit in the treatment of various anxiety disorders with abnormal production of neuroactive steroids. Topics: Allosteric Regulation; Animals; Anxiety; Bridged Bicyclo Compounds, Heterocyclic; Clonazepam; Convulsants; Drug Interactions; Finasteride; Isoquinolines; Male; Mice; Mice, Inbred BALB C; Oxazines; Picrotoxin; Pregnanolone; Progesterone; Receptors, GABA-A; Restraint, Physical; Seizures; Stress, Psychological | 2008 |
Effects of etifoxine on ligand binding to GABA(A) receptors in rodents.
The GABA(A) receptor/chloride ionophore is allosterically modulated by several classes of anxiolytic and anticonvulsant agents, including benzodiazepines, barbiturates and neurosteroids. Etifoxine, an anxiolytic and anticonvulsant compound competitively inhibited the binding of [(35)S]t-butylbicyclophosphoro-thionate (TBPS), a specific ligand of the GABA(A) receptor chloride channel site. To investigate the etifoxine modulatory effects on the different binding sites of the GABA(A) receptor complex, we have examined the effects of etifoxine on binding of the receptor agonist [(3)H]muscimol and the benzodiazepine modulator [(3)H]flunitrazepam in rat brain membrane preparations. The anticonvulsant properties of etifoxine combined with muscimol and flunitrazepam were performed in mice with picrotoxin-induced clonic seizures. Etifoxine modestly enhanced binding of [(3)H]muscimol and of [(3)H]flunitrazepam by increasing the number of binding sites without changing the binding affinity of [(3)H]flunitrazepam. In contrast, the compound decreased the affinity of muscimol for its binding site. In vivo, the combination of subactive doses of etifoxine with muscimol or flunitrazepam produced an anticonvulsant additive effect against the picrotoxin-induced clonic seizures in mice. These results suggest that the interaction of etifoxine on the GABA(A) receptor complex would allosterically modify different binding sites due to conformational changes. Functionally, the resulting facilitation of GABA transmission underlies the pharmacological properties of etifoxine. Topics: Animals; Binding, Competitive; Brain; Cell Membrane; Dose-Response Relationship, Drug; Flunitrazepam; GABA Agonists; GABA Antagonists; GABA Modulators; Male; Mice; Mice, Inbred ICR; Muscimol; Neurons; Oxazines; Rats; Receptors, GABA-A; Seizures; Tritium | 2002 |
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. Topics: Animals; Anti-Anxiety Agents; Anticonvulsants; Benzodiazepines; Benzodiazepinones; Clobazam; Drug Synergism; Male; Mice; Oxazines; Seizures; Valproic Acid | 1986 |
Etifoxine: evaluation of its anticonvulsant profile in mice in comparison with sodium valproate, phenytoin and clobazam.
The anticonvulsant potential of 6-chloro-2-(ethylamino)-4-methyl-4-phenyl-4H-3,1-benzoxazine (etifoxine), a non-benzodiazepine tranquilizer, was evaluated in mice in comparison to valproate, phenytoin and clobazam. Maximal seizures were induced by electroshock (MES) and the chemical convulsants pentetrazol (PTZ), picrotoxin (PTX), bicuculline (BIC), isoniazid (INH), nicotine (NIC) and strychnine (STR). Tonic extensor convulsions were prevented by etifoxine in the following rank order of potency (ED50 values with seizure tests): 39.5 (PTX), 101 (PTZ), 101 (MES), 154 (INH), 181 (NIC), 397 (BIC), and greater than 800 mg/kg p.o. (STR). Clonic seizures were induced by threshold doses of PTZ, PTX and pilocarpine (PIL) and antagonized by etifoxine at ED50 values of 181 (PIL), 221 (PTZ), and greater than 800 mg/kg p.o. (PTX). Hence, etifoxine blocked both tonic and clonic seizures but was more potent against the tonic component. The anticonvulsant profile of etifoxine appeared similar to that of valproate. However, in terms of potency, protective indices (ED50 rotarod/ED50 seizure test) and therapeutic indices (LD50/ED50 seizure test) etifoxine was on an average 3.7, 12 and 14 times superior to valproate, respectively. It is concluded that etifoxine has a marked anticonvulsive potential and may be beneficially used in epileptic disorders, especially of the grand mal type. Topics: Animals; Anti-Anxiety Agents; Anticonvulsants; Benzodiazepines; Benzodiazepinones; Clobazam; Electroshock; Lethal Dose 50; Male; Mice; Oxazines; Phenytoin; Postural Balance; Seizures; Valproic Acid | 1985 |