Can pentylenetetrazole and maximal electroshock rodent seizure models quantitatively predict antiepileptic efficacy in humans?

http://www.ninds.nih.gov/research/asp/index.htm [last accessed 05.08.14]. Yuen, 2014, How predictive are photosensitive epilepsy models as proof of principle trials for epilepsy?, Seizure, 23, 490, 10.1016/j.seizure.2014.03.011 Glauser, 2006, ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes, Epilepsia, 47, 1094, 10.1111/j.1528-1167.2006.00585.x Reith, 2001, Population pharmacokinetic modelling of steady state carbamazepine clearance in children, adolescents, and adults, J Pharmacokinet Pharmacodyn, 28, 79, 10.1023/A:1011569703060 Messina, 2005, Phenobarbital pharmacokinetics in old age: a case-matched evaluation based on therapeutic drug monitoring data, Epilepsia, 46, 372, 10.1111/j.0013-9580.2005.47504.x Wright, 2010, The ‘apparent clearance’ of free phenytoin in elderly vs. younger adults, Br J Clin Pharmacol, 70, 132, 10.1111/j.1365-2125.2010.03673.x Xu, 2011, Pharmacokinetics of carbamazepine polymorphs and dihydrate in rats, related to dogs and humans, Arch Pharm Res, 34, 1973, 10.1007/s12272-011-1118-8 Radulovic, 1995, Disposition of gabapentin (Neurontin) in mice, rats, dogs and monkeys, Drug Metab Dispos, 23, 441 Castel-Branco, 2005, Lamotrigine pharmacokinetic/pharmacodynamics modelling in rats, Fundam Clin Pharmacol, 19, 669, 10.1111/j.1472-8206.2005.00380.x Kapetanovic, 1982, Phenobarbital pharmacokinetics in rat as a function of age, Durg Metab Dispos, 10, 586 Jolivette, 2005, Extrapolation of human pharmacokinetic parameters from rat, dog and monkey data: molecular properties associated with extrapolative success or failure, J Pharm Sci, 94, 1467, 10.1002/jps.20373 Markowitz, 2010, The pharmacokinetics of commonly used antiepileptic drugs in immature CD1 mice, Neuroreport, 21, 452, 10.1097/WNR.0b013e328338ba18 Akula, 2009, Effect of various antiepileptic drugs in a pentylenetetrazol-induced seizure model in mice, Methods Find Exp Clin Pharmacol, 31, 423, 10.1358/mf.2009.31.7.1415891 Andres-Mach, 2012, Effect of ACEA – a selective cannabinoid CB1 receptor agonist on the protective action of different antiepileptic drugs in the mouse pentylenetetrazole-induced seizure model, Prog Neuropsychopharmacol Biol Psychiatry, 39, 301, 10.1016/j.pnpbp.2012.07.001 Assi, 2001, N6-cyclohexyladenosine and 3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid enhance the effect of antiepileptic drugs against induced seizures in mice, J Pharm Pharm Sci, 4, 42 Balakrishnan, 1999, Anticonvulsant profile of nimodipine and nitrendipine against pentylenetetrazole induced seizures in rats, Indian J Exp Biol, 37, 340 Beekman, 1998, Reversal of behavioural effects of pentylenetetrazol by the neuroactive steroid ganaxolone, J Pharmacol Exp Ther, 284, 868 Borowicz, 2000, 7-Nitroindazole, a nitric oxide synthase inhibitor, enhances the anticonvulsive action of ethosuximide and clonazepam against pentylenetetrazole-induced convulsions, J Neural Transm, 107, 1117, 10.1007/s007020070025 Borowicz, 2004, Isobolographic and subthreshold analysis of interactions among felbamate and four conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice, Epilepsia, 45, 1176, 10.1111/j.0013-9580.2004.09604.x Borowicz, 2012, Effects of fluoxetine on the anticonvulsant action of valproate and ethosuximide in mouse model of myoclonic convulsions, Ann Agric Environ Med, 19, 487 Cuadrado, 2005, Beneficial interaction between vigabatrin and valproate against seizures induced by pentylenetetrazole in mice, Pharm Res, 51, 489, 10.1016/j.phrs.2004.12.006 Dudra-Jastrzebska, 2009, Isobolographic characterization of the anticonvulsant interaction profiles of levetiracetam in combination with clonazepam, ethosuximide, phenobarbital and valproate in the mouse pentylenetetrazole-induced seizure model, Seizure, 18, 607, 10.1016/j.seizure.2009.06.009 El-Azab, 2012, Synthesis and anticonvulsant evaluation of some new 2,3,8-trisubstituted-4(3H)-quinazoline derivatives, Bioorg Med Chem Lett, 22, 327, 10.1016/j.bmcl.2011.11.007 Elmazar, 1992, Anticonvulsant and neurotoxic activities of twelve analogues of valproic acid, J Pharm Sci, 82, 1255, 10.1002/jps.2600821214 Gasior, 2000, Acute and chronic effects of the synthetic neuroactive steroid, ganaxolone, against the convulsive and lethal effects of pentylenetetrazole in seizure-kindled mice: comparison with diazepam and valproate, Neuropharmacology, 39, 1184, 10.1016/S0028-3908(99)00190-2 Gravemann, 2008, Hydroxamic acid and fluorinated derivatives of valproic acid. Anticonvulsant activity, neurotoxicity and teratogenicity, Neurotox Teratol, 30, 390, 10.1016/j.ntt.2008.03.060 Kaminski, 2008, Amlodipine enhances the activity of antiepileptic drugs against pentylenetetrazole-induced seizures, Pharmacol Biochem Behav, 68, 661, 10.1016/S0091-3057(01)00468-3 Luszczki, 2004, Isobolographic profile of interactions between tiagabine and gabapentin: a preclinical study, Arch Pharmacol, 369, 434, 10.1007/s00210-004-0867-z Luszczki, 2005, Isobolographic characterisation of interactions among selected newer antiepileptic drugs in the mouse pentylenetetrazole-induced seizure model, Arch Pharmacol, 372, 41, 10.1007/s00210-005-1088-9 Luszczki, 2005, Pharmacodynamic and/or pharmacokinetic characteristics of interactions between loreclezole and four conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice: an isobolographic analysis, Epilepsy Behav, 7, 639, 10.1016/j.yebeh.2005.07.007 Luszczki, 2006, Characterization of the anticonvulsant, behavioural and pharmacokinetic interaction profiles of stiripentol in combination with clonazepam, ethosuximide, phenobarbital and valproate using isobolographic analysis, Epilepsia, 47, 1841, 10.1111/j.1528-1167.2006.00825.x Luszczki, 2006, Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures in mice, Pharmacol Rep, 58, 658 Luszczki, 2007, Effect of NG-nitro-l-arginine on the anticonvulsant action of four second-generation antiepileptic drugs in pentetrazole-induced clonic seizures in mice, Pharmacol Rep, 59, 467 Luszczki, 2009, Isobolographic analysis of interaction between oxcarbazepine and valproate in pentylenetetrazole-induced seizures in mice, J Preclin Clin Res, 2, 40 Luszczki, 2011, Effects of WIN 55,212-2 mesylate (a synthetic cannabinoid) on the protective action of clonazepam, ethosuximide, phenobarbital and valproate against pentylenetetrazole-induced clonic seizures in mice, Prog Neuropsychopharmacol Biol Psychiatry, 35, 1870, 10.1016/j.pnpbp.2011.07.001 Nieoczym, 2012, Influence of sildenafil on the anticonvulsant action of selected antiepileptic drugs against pentylenetetrazole-induced clonic seizures in mice, J Neural Transm, 119, 923, 10.1007/s00702-012-0767-1 Russo, 2004, Nifedipine affects the anticonvulsant activity of topiramate in various animal models of epilepsy, Neuropharmacology, 46, 865, 10.1016/j.neuropharm.2003.11.028 Sood, 2008, Dose-finding study with nicotine as a proconvulsant agent in PTZ-induced seizure model in mice, J Biomed Sci, 15, 755, 10.1007/s11373-008-9272-9 Thakur, 2011, Experimental re-evaluation of flunarizine as add-on antiepileptic therapy, J Pharm Bioallied Sci, 3, 253, 10.4103/0975-7406.80782 Andurkar, 1999, The anticonvulsant activities of N-benzyl 3-methoxypropionamides, Bioorg Med Chem, 7, 2381, 10.1016/S0968-0896(99)00186-8 Balakrishnan, 1998, Effect of nimodipine on the efficacy of commonly used antiepileptic drugs in rats, Indian J Exp Biol, 36, 51 Bialer, 2004, Correlation analysis between anticonvulsant ED50 values of antiepileptic drugs in mice and rats and their therapeutic doses and plasma levels, Epilepsy Behav, 5, 866, 10.1016/j.yebeh.2004.08.021 Borowicz, 2006, Fluoxetine enhances the anticonvulsant effects of conventional antiepileptic drugs in maximal electroshock seizures in mice, Pharmacol Rep, 58, 83 Borowicz, 2007, Interactions between zonisamide and conventional antiepileptic drugs in the mouse maximal electroshock test model, Eur Neuropsychopharmacol, 17, 265, 10.1016/j.euroneuro.2006.06.008 Chen, 2007, Synthesis and anticonvulsant evaluation of 4-(4-alkoxylphenyl)-3-ethyl-4H-1,2,4-triazoles as open-chain analogues of 7-alkoxyl-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolines, Bioorg Med Chem, 15, 6775, 10.1016/j.bmc.2007.08.004 Clark, 1985, Anticonvulsant activity of some 4-aminobenzanilides, J Med Chem, 28, 1259, 10.1021/jm00147a024 Czuczwar, 1990, Influence of different methylxanthines on the anticonvulsant action of common antiepileptic drugs in mice, Epilepsia, 31, 318, 10.1111/j.1528-1157.1990.tb05382.x Deng, 2010, Design and synthesis of 10-alkoxy-5, 6-dihydro-triazolo[4,3-d]benzo[f][1,4]oxazepine derivatives with anticonvulsant activity, Eur J Med Chem, 45, 3080, 10.1016/j.ejmech.2010.03.041 Fischer, 1992, Anticonvulsant and sodium channel blocking effects of ralitoline in different screening models, Arch Pharmacol, 346, 442, 10.1007/BF00171088 Flaherty, 1996, Synthesis and evaluation of N-(phenylacetyl)trifluoromethanesulfonamides as anticonvulsant agents, J Med Chem, 39, 1509, 10.1021/jm950761q Garske, 1991, Preclinical profile of the anticonvulsant remacemide and its enantiomers in the rat, Epilepsy Res, 9, 161, 10.1016/0920-1211(91)90050-P Gasior, 1996, Anticonvulsant activity of phenobarbital and valproate against maximal electroshock in mice during chronic treatment with caffeine and caffeine discontinuation, Epilepsia, 37, 262, 10.1111/j.1528-1157.1996.tb00023.x Geurts, 1998, N-(benzyloxycarbonyl)glycine esters and amides as new anticonvulsants, J Med Chem, 41, 24, 10.1021/jm970086f Guan, 2009, Evaluation of anticonvulsant activity of QUAN-0806 in various murine experimental seizure models, Pharmazie, 64, 248 Guo, 2009, Design and synthesis of 5-alkoxy-[1,2,4]triazolo[4,3-a]quinoline derivatives with anticonvulsant activity, Eur J Med Chem, 44, 954, 10.1016/j.ejmech.2008.07.010 Gupta, 2004, Modulation of antiepileptic effect of phenytoin and carbamazepine by melatonin in mice, Methods Find Exp Clin Pharmacol, 26, 99, 10.1358/mf.2004.26.2.800061 Lambert, 2001, Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice, Epilepsia, 42, 321, 10.1046/j.1528-1157.2001.41499.x Leander, 1992, Fluoxetine, a selective serotonin-uptake inhibitor, enhances the anticonvulsant effects of phenytoin, carbamazepine, and ameltolide (LY201116), Epilepsia, 33, 573, 10.1111/j.1528-1157.1992.tb01712.x Lu, 2001, Synergistic protection of allopregnanolone and phenobarbital against maximal electroshock seizures in mice, Acta Pharmacol Sin, 22, 361 Lukawski, 2009, Effect of ethacrynic acid on the anticonvulsant activity of the second-generation antiepileptics against maximal electroshock-induced seizures in mice, Epilepsy Res, 87, 190, 10.1016/j.eplepsyres.2009.08.016 Lukawski, 2010, Influence of ethacrynic acid on the anticonvulsant activity of conventional antiepileptic drugs in the mouse maximal electroshock seizure model, Pharmacol Rep, 62, 808, 10.1016/S1734-1140(10)70341-8 Lukawski, 2011, Interactions between ACE inhibitors and classical antiepileptic drugs in the mouse maximal electroshock seizures, Pharmacol Biochem Behav, 100, 152, 10.1016/j.pbb.2011.06.030 Lukawski, 2012, Effect of hydrochlorothiazide on the anticonvulsant action of antiepileptic drugs against maximal electroshock-induced seizures in mice, Pharmacol Rep, 64, 315, 10.1016/S1734-1140(12)70770-3 Luszczki, 2010, Interactions of stiripentol with clobazam and valproate in the mouse maximal electroshock-induced seizure model, Epilepsy Res, 90, 188, 10.1016/j.eplepsyres.2010.04.006 Luszczki, 2003, Interactions of lamotrigine with topiramate and first-generation antiepileptic drugs in the maximal electroshock test in mice: an isobolographic analysis, Epilepsia, 44, 1003, 10.1046/j.1528-1157.2003.10003.x Luszczki, 2005, Pharmacodynamic and pharmacokinetic interaction studies of loreclezole with felbamate, lamotrigine, topiramate, and oxcarbazepine in the mouse maximal electroshock seizure model, Epilepsia, 46, 344, 10.1111/j.0013-9580.2005.34704.x Luszczki, 2006, Gabapentin synergistically interacts with topiramate in the mouse maximal electroshock seizure model: an isobolographic analysis, Pharmacol Rep, 58, 944 Luszczki, 2006, 7-Nitroindazole enhances dose-dependently the anticonvulsant activities of conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model, Pharmacol Rep, 58, 1734 Luszczki, 2007, Furosemide potentiates the anticonvulsant action of valproate in the mouse maximal electroshock seizure model, Epilepsy Res, 76, 66, 10.1016/j.eplepsyres.2007.06.010 Luszczki, 2008, Agmatine enhances the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshock seizure model, J Neural Transm, 115, 1485, 10.1007/s00702-008-0046-3 Luszczki, 2009, Amiloride enhances the anticonvulsant action of various antiepileptic drugs in the mouse maximal electroshock seizure model, J Neural Transm, 116, 57, 10.1007/s00702-008-0152-2 Luszczki, 2010, Additive interactions of pregabalin with lamotrigine, oxcarbazepine and topiramate in the mouse maximal electroshock-induced seizure model: A type I isobolographic analysis for non-parallel dose–response relationship curves, Epilepsy Res, 91, 166, 10.1016/j.eplepsyres.2010.07.009 Luszczki, 2010, Interactions of 1-methyl-1,2,3,4-tetrahydroisoquinoline with lamotrigine, oxcarbazepine, pregabalin, and topiramate in the mouse maximal electroshock-induced seizure model: a type I isobolographic analysis, Epilepsy Res, 89, 207, 10.1016/j.eplepsyres.2010.01.001 Luszczki, 2011, Synthetic cannabinoid WIN 55,212-2 mesylate enhances the protective action of four classical antiepileptic drugs against maximal electroshock-induced seizures in mice, Pharmacol Biochem Behav, 98, 261, 10.1016/j.pbb.2011.01.002 Luszczki, 2003, Interactions between oxcarbazepine and conventional antiepileptic drugs in the maximal electroshock test in mice: an isobolographic analysis, Epilepsia, 44, 489, 10.1046/j.1528-1157.2003.32702.x Luszczki, 2004, Preclinical profile of combinations of some second-generation antiepileptic drugs: an isobolographic analysis, Epilepsia, 45, 895, 10.1111/j.0013-9580.2004.05104.x Luszczki, 2006, Isobolographic analysis of interactions between loreclezole and conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model, Arch Pharmacol, 373, 169, 10.1007/s00210-006-0055-4 Luszczki, 2006, Pharmacodynamic and pharmacokinetic characterization of interactions between levetiracetam and numerous antiepileptic drugs in the mouse maximal electroshock seizure model: an isobolographic analysis, Epilepsia, 47, 10, 10.1111/j.1528-1167.2006.00364.x Luszczki, 2006, 1-Methyl-1,2,3,4-tetrahydroisoquinoline enhances the anticonvulsant action of carbamazepine and valproate in the mouse maximal electroshock seizure model, Neuropharmacology, 50, 133, 10.1016/j.neuropharm.2005.07.016 Luszczki, 2006, Influence of NG-nitro-l-arginine on the anticonvulsant and acute adverse effects of some newer antiepileptic drugs in the maximal electroshock-induced seizures and chimney test in mice, Pharmacol Rep, 58, 955 Luszczki, 2006, Biphasic characteristic of interactions between stiripentol and carbamazepine in the mouse maximal electroshock-induced seizure model: a three-dimensional isobolographic analysis, Arch Pharmacol, 374, 51, 10.1007/s00210-006-0100-3 Luszczki, 2008, Influence of imperatorin on the anticonvulsant activity and acute adverse-effect profile of lamotrigine in maximal electroshock-induced seizures and chimney test in mice, Pharmacol Rep, 60, 566 Luszczki, 2008, Effects of amlodipine, diltiazem, and verapamil on the anticonvulsant action of topiramate against maximal electroshock-induced seizures in mice, Can J Physiol Pharmacol, 86, 113, 10.1139/Y08-007 Luszczki, 2009, Isobolographic characterization of interactions of retigabine with carbamazepine, lamotrigine, and valproate in the mouse maximal electroshock-induced seizure model, Arch Pharmacol, 379, 163, 10.1007/s00210-008-0349-9 Marona, 1998, Synthesis and anticonvulsant activity of 1,2-aminoalkanol derivatives, Acta Poloniae Pharmaceut, 55, 487 Marona, 2003, Preliminary evaluation of anticonvulsant activity of some 4-(benzyloxy)-benzamides, Acta Pol Pharm, 60, 477 Maryanoff, 1998, Structure-activity studies on anticonvulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives, J Med Chem, 41, 1315, 10.1021/jm970790w Matagne, 1998, Validation of corneally kindled mice: a sensitive screening model for partial epilepsy in man, Epilepsy Res, 31, 59, 10.1016/S0920-1211(98)00016-3 Mulzac, 1993, Profile of anticonvulsant activity and minimal toxicity of methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1-oate and some prototype antiepileptic drugs in mice and rats, Epilepsia, 34, 1141, 10.1111/j.1528-1157.1993.tb02147.x Nieoczym, 2010, Effect of sildenafil on the anticonvulsant action of classical and second-generation antiepileptic drugs in maximal electroshock-induced seizures in mice, Epilepsia, 51, 1552, 10.1111/j.1528-1167.2009.02485.x Pandeya, 1998, Anticonvulsant activity of thioureido derivatives of acetophenone semicarbazone, Pharm Res, 37, 17, 10.1006/phrs.1997.0250 Porter, 1984, Antiepileptic drug development program, Cleveland Clin Q, 51, 293, 10.3949/ccjm.51.2.293 Raju, 1999, Effect of fluoxetine on maximal electroshock seizures in mice: acute vs chronic administration, Pharm Res, 39, 451, 10.1006/phrs.1999.0466 Rao, 2005, Anticonvulsant and neurotoxicity profile of Nardostachys jatamansi in rats, J Ethnopharmacol, 102, 351, 10.1016/j.jep.2005.06.031 Shek, 1989, Improved anticonvulsant activity of phenytoin by a redox brain delivery system. III: Brain uptake and pharmacological effects, J Pharm Sci, 78, 837, 10.1002/jps.2600781012 Shenoy, 1982, Comparative anticonvulsant activity and neurotoxicity of clobazam, diazepam, phenobarbital, and valproate in mice and rats, Epilepsia, 23, 399, 10.1111/j.1528-1157.1982.tb05426.x Shindikar, 2006, Design, synthesis and in vivo anticonvulsant screening in mice of novel phenylacetamides, Eur J Med Chem, 41, 786, 10.1016/j.ejmech.2006.03.013 Stagnitto, 1990, Preclinical profile of remacemide: a novel anticonvulsant effective against maximal electroshock seizures in mice, Epilepsy Res, 7, 11, 10.1016/0920-1211(90)90050-6 Sun, 2010, Evaluation of the anticonvulsant activity of 6-(4-chlorophenyoxy)-tetrazolo[5,1-a]phthalazine in various experimental seizure models in mice, Pharmacol Rep, 62, 273, 10.1016/S1734-1140(10)70266-8 Swiader, 2003, Interaction of astemizole, an H1 receptor antagonist, with conventional antiepileptic drugs in mice, Pharmacol Biochem Behav, 76, 169, 10.1016/S0091-3057(03)00212-0 Swiader, 2005, Effects of some convulsant agents on the protective activity of topiramate against maximal electroshock-induced seizures in mice, Pharmacol Rep, 57, 373 Swinyard, 1993, Characterisation of the anticonvulsant properties of F-721, Epilepsy Res, 15, 35, 10.1016/0920-1211(93)90007-T Tomczyk, 2007, Enhanced glutamatergic transmission reduces the anticonvulsant potential of lamotrigine but not of felbamate against tonic–clonic seizures, Pharmacol Rep, 59, 462 Wlaz, 1993, Influence of chronic aminophylline on the anticonvulsant efficacy of phenobarbital and valproate in mice, Epilepsia, 34, 385, 10.1111/j.1528-1157.1993.tb02426.x Zarnowska, 2009, Pharmacodynamic and pharmacokinetic interactions between common antiepileptic drugs and acetone, the chief anticonvulsant ketone body elevated in the ketogenic diet in mice, Epilepsia, 50, 1132, 10.1111/j.1528-1167.2008.01864.x Zhang, 2010, Synthesis and anticonvulsant activity of some 7-alkoxy-2H-1,4-benzothiazin-3(4H)-ones and 7-Alkoxy-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazines, Chem Pharm Bull, 58, 326, 10.1248/cpb.58.326 Bailleux, 1995, Comparative anticonvulsant activity and neurotoxicity of 4-amino-N-(2,6-Dimethylphenyl)phthalimide and prototype antiepileptic drugs in mice and rats, Epilepsia, 36, 559, 10.1111/j.1528-1157.1995.tb02567.x Bailleux, 1995, Synthesis and anticonvulsant activity of some 4-nitro-N-phenylbenzamides, Eur J Med Chem, 30, 1439, 10.1016/0223-5234(96)88254-7 Clark, 1998, Comparative anticonvulsant activity and neurotoxicity of 4-amino-N-(2,6-dimethylphenyl)benzamide and prototype antiepileptic drugs in mice and rats, Epilepsia, 29, 198, 10.1111/j.1528-1157.1988.tb04420.x Loscher, 1991, The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. IV. Protective indices, Epilepsy Res, 9, 1, 10.1016/0920-1211(91)90041-D Dalby, 1997, Comparison of the preclinical anticonvulsant profiles of tiagabine, lamotrigine, gabapentin and vigabatrin, Epilepsy Res, 28, 63, 10.1016/S0920-1211(97)00031-4 Diouf, 1997, Anticonvulsant and neurotoxicological properties of 4-amino-N-(2-ethylphenyl)benzamide, a potent ameltolide analogue, Biomed Pharmacother, 51, 131, 10.1016/S0753-3322(97)86911-9 Jin, 2006, Anticonvulsant and toxicity evaluation of some 7-alkoxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-1(2H)-ones, Bioorg Med Chem, 14, 6868, 10.1016/j.bmc.2006.06.044 Kehne, 1997, Preclinical characterization of MDL 27,192 as a potential broad spectrum anticonvulsant agent with neuroprotective properties, Epilepsy Res, 27, 41, 10.1016/S0920-1211(96)01020-0 Kruse, 1985, Etifoxine: evaluation of its anticonvulsant profile in mice in comparison with sodium valproate, phenytoin and clobazam, Arzneim-Forsch, 35, 133 Luszczki, 2005, Pharmacological and behavioral characteristics of interactions between vigabatrin and conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice: an isobolographic analysis, Neuropsychopharmacology, 30, 958, 10.1038/sj.npp.1300602 Masereel, 1998, Design, synthesis, and anticonvulsant activity of 1-(pyrid-3-ylsulfonamido)-2-nitroethylenes, J Med Chem, 41, 3239, 10.1021/jm981022n Miller, 1986, Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: I. Anticonvulsant profile in mice and rats, Epilepsia, 27, 483, 10.1111/j.1528-1157.1986.tb03572.x Obniska, 2012, Synthesis and anticonvulsant properties of new mannich bases derived from 3,3-disubstituted pyrrolidine-2,5-diones. Part IV, Arch Pharm Chem Life Sci, 345, 713, 10.1002/ardp.201200092 Piao, 2012, Synthesis and biological evaluation of 9-alkoxy-6,7-dihydro-5H-benzo[c] [1,2,4]triazolo[4,3-a]azepines as potential anticonvulsant agents, Arzneimittelforschung, 62, 202, 10.1055/s-0031-1301295 Raza, 2008, Potentiation of valproate-induced anticonvulsant response by Nigella sativa seed constituents: the role of GABA receptors, Int J Health Sci, 2, 15 Rostock, 1996, D-23129: a new anticonvulsant with a broad spectrum activity in animal models of epileptic seizures, Epilepsy Res, 23, 211, 10.1016/0920-1211(95)00101-8 Rowley, 2010, Comparative anticonvulsant efficacy in the corneal kindled mouse model of partial epilepsy: correlation with other seizure and epilepsy models, Epilepsy Res, 92, 163, 10.1016/j.eplepsyres.2010.09.002 Shank, 1994, Topiramate: preclinical evaluation of a structurally novel anticonvulsant, Epilepsia, 35, 450, 10.1111/j.1528-1157.1994.tb02459.x Swinyard, 1986, Comparative anticonvulsant activity and neurotoxicity of felbamate and four prototype antiepileptic drugs in mice and rats, Epilepsia, 27, 27, 10.1111/j.1528-1157.1986.tb03497.x Swinyard, 1991, Anticonvulsant profiles of the potent and orally active GABA uptake inhibitors SK&F 89976-A and SK&F 100330-A and four prototype antiepileptic drugs in mice and rats, Epilepsia, 32, 569, 10.1111/j.1528-1157.1991.tb04694.x Tantisira, 1997, Preliminary evaluation of the anticonvulsant activity of a valproic acid analog: N-(2-propylpentanoyl) urea, Res Comm Mol Pathol Pharmacol, 97, 151 Ulloque, 1986, Effects of γ-aminobutyric acid (GABA) receptor agonists on the neurotoxicity and anticonvulsant activity of barbiturates in mice, J Pharmacol Exp Ther, 237, 488 Wei, 2009, Synthesis of 2-substituted-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles as potential anticonvulsant agents, Arch Pharm Res, 32, 23, 10.1007/s12272-009-1114-4 White, 1997, Topiramate enhances GABA-mediated chloride flux and GABA-evoked chloride currents in murine brain neurons and increases seizure threshold, Epilepsy Res, 28, 167, 10.1016/S0920-1211(97)00045-4 White, 2008, The anticonvulsant profile of rufinamide (CGP 33101) in rodent seizure models, Epilepsia, 49, 1213, 10.1111/j.1528-1167.2008.01552.x Yamashita, 2004, Effects of 2-[N-(4-chlorophenyl)-N-methylamino]-4Hpyrido[3.2-e]-1,3-thiazin-4-one (YM928), an orally active alpha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, in models of generalized epileptic seizure in mice and rats, J Pharmacol Exp Ther, 308, 127, 10.1124/jpet.103.058495 Zelger, 1983, New anticonvulsants derived from 4-allyl-2-methoxyphenol (eugenol): comparison with common antiepileptics in mice, Pharmacology, 27, 40, 10.1159/000137828 Dingemanse, 1989, Pharmacokinetic modelling of the anticonvulsant action of phenobarbital in rats, J Pharmacol Exp Ther, 249, 601 Della Paschoa, 2000, Pharmacokinetic-pharmacodynamic correlation of lamotrigine, flunarizine, loreclezole, CGP40116 and CGP39551 in the cortical stimulation model, Epilepsy Res, 40, 41, 10.1016/S0920-1211(00)00102-9