Progress report on new antiepileptic drugs: A summary of the Ninth Eilat Conference (EILAT IX)

Epilepsy Research

Volumn 83, Issue 1, 2009, Pages 1-43

  Bialer, Meir ^a   Johannessen, Svein I ^b   Levy, René H ^c   Perucca, Emilio ^d   Tomson, Torbjörn ^e   White, H Steve ^f  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b OSLO UNIVERSITY HOSPITAL   (Norway)

^c UNIVERSITY OF WASHINGTON   (United States)

^d UNIVERSITY OF PAVIA   (Italy)

^e KAROLINSKA INSTITUTE   (Sweden)

^f UNIVERSITY OF UTAH   (United States)

Author keywords

Antiepileptic drugs; Clinical trials; Conference; Drug development; Epilepsy; Pharmacology

Indexed keywords

1,3 DIMETHOXYMETHYL 5,5 DIPHENYLBARBITURIC ACID; 2 ISOPROPYLVALERAMIDE; ANTICONVULSIVE AGENT; BRIVARACETAM; CARBAMAZEPINE; CARBAMIC ACID 2 (2 CHLOROPHENYL) 2 HYDROXYETHYL ESTER; CARISBAMATE; CLONAZEPAM; DEOXYGLUCOSE; DIAZEPAM; DIGOXIN; ESLICARBAZEPINE ACETATE; ETIRACETAM; GABAPENTIN; GANAXOLONE; HARKOSERIDE; HUPERZINE A; JZP 4; LAMOTRIGINE; NAX 5055; PHENYTOIN; PLACEBO; RETIGABINE; T 2000; TOLBUTAMIDE; TONABERSAT; TOPIRAMATE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID; VALROCEMIDE; WARFARIN; YKP 3089;

ABDOMINAL PAIN; ANOREXIA; ANTICONVULSANT ACTIVITY; AREA UNDER THE CURVE; ATAXIA; BLURRED VISION; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL TRIAL; CONFUSION; CONVULSION; COORDINATION DISORDER; DIPLOPIA; DIZZINESS; DRUG ABSORPTION; DRUG ANTAGONISM; DRUG BINDING; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INHIBITION; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENTIATION; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSARTHRIA; EPILEPSY; EPILEPTIC STATE; EPILEPTOGENESIS; ERECTILE DYSFUNCTION; EYE INFLAMMATION; FATIGUE; GAIT DISORDER; GASTROINTESTINAL SYMPTOM; GENOTOXICITY; HEADACHE; HUMAN; HYPONATREMIA; INSOMNIA; MIGRAINE; NAUSEA; NONHUMAN; PATIENT COMPLIANCE; PRIORITY JOURNAL; RASH; REPEATED DRUG DOSE; REVIEW; RHINOPHARYNGITIS; SEIZURE; SIDE EFFECT; SINGLE DRUG DOSE; SLEEP DISORDER; SOMNOLENCE; TERATOGENICITY; THROAT DISEASE; THROAT INFLAMMATION; TREMOR; UNSPECIFIED SIDE EFFECT; URINARY HESITANCY; URINARY TRACT INFECTION; VERTIGO; VOMITING;

ANIMALS; ANTICONVULSANTS; EPILEPSY; HUMANS;

EID: 57849141134     PISSN: 09201211     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.eplepsyres.2008.09.005     Document Type: Review

References (150)

1. Adkins E.M., Smith M.D., Pruess T., Grussendorf E., Green B., Bulaj G., and White H.S. NAX-5055: a metabolically stable galanin-based neuropeptide with potent anticonvulsant and antinociceptive actions. Epilepsia 48 Suppl. 6 (2007) 292
2. Alles G.A., Ellis C.H., Feigen G.A., and Redemann M.A. Comparative central depressant actions of some 5-phenyl-5-alkyl barbituric acids. J. Pharmacol. Exp. Ther. 89 (1947) 356-367
3. Almeida L., and Soares-da-Silva P. Eslicarbazepine acetate (BIA 2-093). Neurotherapeutics 4 (2007) 88-96
4. Almeida L., Potgieter J.H., Maia J., Potgieter M.A., Mota F., and Soares-da-Silva P. Pharmacokinetics of eslicarbazepine acetate in patients with moderate hepatic impairment. Eur. J. Clin. Pharmacol. 64 (2008) 267-273
5. Almeida, L., Bialer, M., Soares-da-Silva, P., in press. Eslicarbazepine acetate. In: Shorvon, S., Perucca, E., Engel, J. (Eds.), Treatment of Epilepsy, 3rd ed., Wiley-Blackwell, Oxford, UK.
6. Amann B., Sterr A., Vieta E., Stampfer R., Walden J., and Grunze H. An exploratory open trial on safety and efficacy of the anticonvulsant retigabine in acute manic patients. J. Clin. Psychopharmacol. 26 (2006) 534-536
7. Armand V., Rundfeldt C., and Heinemann U. Effects of retigabine (D-23129) on different patterns of epileptiform activity induced by 4-aminopyridine in rat entorhinal cortex hippocampal slices. Naunyn-Schmiedeberg's Arch. Pharmacol. 359 (1999) 33-39
8. Barton M.E., Klein B.D., Wolf H.H., and White S.H. Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy. Epilepsy Res. 47 (2001) 217-227
9. Ben-Menachem E., Biton V., Jatuzis D., Abou-Khalil B., Doty P., and Rudd G.D. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia 48 (2007) 1308-1317
10. Berwick J., Johnston D., Jones M., Martindale J., Martin C., Kennerly A.J., Redgrave P., and Mayhew J.E. Fine detail of neurovascular coupling revealed by spatio-temporal analysis of the hemodynamic response to single whisker stimulation in rat barrel cortex. J. Neurophysiol. 99 (2008) 787-798
11. Biagini G., Baldelli E., Longo D., Pradelli L., Zini I., Rogawski M.A., and Avoli M. Endogenous neurosteroids modulate epileptogenesis in a model of temporal lobe epilepsy. Exp. Neurol. 201 (2006) 519-524
12. Biagini, G., Longo, D., Baldelli, E., Zoli, M., Rogawski, M.A., Bertazzoni G., Avoli, M., in press. Neurosteroids and epileptogenesis in the pilocarpine model: evidence for a relationship between P450scc induction and length of the latent period. Epilepsia.
13. Bialer M. Clinical pharmacology of valpromide. Clin. Pharmacokinet. 20 (1991) 114-122
14. Bialer M. New antiepileptic drugs that are second generation to existing antiepileptic drugs. Expert Opin. Investig. Drugs 15 (2006) 637-647
15. Bialer M., and Yagen B. Valproic acid-second generation. Neurotherapeutics 4 (2007) 130-137
16. Bialer M., Johannessen S., Kupferberg H.J., Levy R.H., Loiseau P., and Perucca E. Progress report on new antiepileptic drugs: a summary of the Sixth Eilat Conference (EILAT VI). Epilepsy Res. 51 (2002) 31-71
17. Bialer M., Johannessen S.I., Kupferberg H.J., Levy R.H., Loiseau P., and Perucca E. Progress report on new antiepileptic drugs: a summary of the fourth Eilat conference (EILAT IV). Epilepsy Res. 34 (2004) 1-41
18. Bialer M., Johannessen S., Kupferberg H.J., Levy R.H., Perucca E., and Tomson T. Progress report on new antiepileptic drugs: a summary of the Eighth Eilat Conference (EILAT VIII). Epilepsy Res. 73 (2007) 1-52
19. Blackburn-Munro G., and Jensen B.S. The anticonvulsant retigabine attenuates nociceptive behaviours in rat models of persistent and neuropathic pain. Eur. J. Pharmacol. 460 (2003) 109-116
20. Brandt C., Heile A., Potschka H., Stoehr T., and Loscher W. Effects of the novel antiepileptic drug lacosamide on the development of amygdala kindling in rats. Epilepsia 47 (2006) 1803-1809
21. Brodsky A., Costantini C., and von Rosenstiel P. Safety and tolerability of brivaracetam (UCB 34714) as adjunctive treatment in adults with refractory partial-onset seizures. Epilepsia 48 Suppl. 6 (2007) 342
22. Bulaj, G., Green, B.R., Lee H-K., Roberston, C.R., White, K., Zhang, L., Sochanska, M., Flynn, S.P., Scholl, E.A., Pruess, T.H., Smith, M.D., White, H.S. Design, synthesis and characterization of high-affinity, systemically-active galanin analogs with potent anticonvulsant activities. J. Med. Chem., 2008, in press.
23. A receptor. J. Pharmacol. Exp. Ther. 280 (1997) 1284-1295
24. Cawello W., Kropeit D., SchiltmeyerB, Hammes W., and Horstmann R. Food does not affect the pharmacokinetics of SPM 927. Epilepsia 45 Suppl. 7 (2004) 307 (Abstract 2.342)
25. Chan W.N., Evans J.M., Hadley M.S., Herdon H.J., Jerman J.C., Parsons A.A., Read S.J., Stean T.O., Thompson M., and Upton N. Identification of (-)-cis-6-acetyl-4S-(3-choro-4-Fluoro-benzoylamino)-3,4-dihydro-2,2-dime thyl-2H-benzo-[b]pyran-3S-ol as a potential antimigraine agent. Bioorg. Med. Chem. Lett. 2 (1999) 285-290
26. Chien S., Bialer M., Solanki B., Verhaeghe T., Doose D.R., Novak G., and Yao C. Pharmacokinetic interaction study between the new antiepileptic and CNS drug RWJ-333369 and carbamazepine in healthy adults. Epilepsia 47 (2006) 1830-1840
27. Chien S., Yao C., Mertens A., Verhaeghe T., Solanki B., Doose D.R., Novak G., and Bialer M. An interaction study between the new antiepileptic and CNS drug carisbamate (RWJ-333369) and lamotrigine and valproic acid. Epilepsia 48 (2007) 1328-1338
28. Chung S., Sperling M., Biton V., Krauss G., Doty P., Sullivan T., and the SP754 Study Group. Lacosamide: efficacy and safety as oral adjunctive therapy in adults with partial-onset seizures. Epilepsia 48 Suppl. 7 (2007) 57
29. Czech T., Yang J.W., Csaszar E., Kappler J., Baumgartner C., and Lubec G. Reduction of hippocampal collapsin response mediated protein-2 in patients with mesial temporal lobe epilepsy. Neurochem. Res. 29 (2004) 2189-2196
30. Dost R., and Rundfeldt C. The anticonvulsant retigabine potently suppresses epileptiform discharges in the low Ca++ and low Mg++ model in the hippocampal slice preparation. Epilepsy Res. 38 (2000) 53-66
31. Dost R., Rostock A., and Rundfeldt C. The anti-hyperalgesic activity of retigabine is mediated by KCNQ potassium channel activation. Naunyn-Schmiedeberg's Arch. Pharmacol. 369 (2004) 382-390
32. Doty P., Rudd G.D., Stoehr T., and Thomas D. Lacosamide. Neurotherapeutics 4 (2007) 145-148
33. Dretchen K.L., Bowles A.M., and Raines A. Protection by phenytoin and calcium channel blocking agents against the toxicity of diisopropylfluorophosphate. Toxicol. Appl. Pharmacol. 83 (1986) 584-589
34. Elger C., Bialer M., Cramer J.A., Maia J., Almeida L., and Soares-da-Silva P. Eslicarbazepine acetate: a double-blind, add-on, placebo-controlled exploratory trial in adult patients with partial-onset seizures. Epilepsia 48 (2007) 497-504
35. Errington A.C., Coyne L., Stöhr T., Selve N., and Lees G. Seeking a mechanism of action for the novel anticonvulsant lacosamide. Neuropharmacology 50 (2006) 1016-1029
36. Foreman M., Hanania T., Stratton S., Wilcox K., White H.S., Stables J., and Eller M. In vivo pharmacological effects of JZP-4, a novel anticonvulsant, in models for anticonvulsant, antimania and antidepressant activity. Pharmacol. Biochem. Behav. 89 (2008) 523-534
37. Francois J., Ferrandon A., Koning E., and Nehlig A. A new drug, RWJ-33369, protects limbic areas in the lithium-pilcarpine model (lipilo) of epilepsy and delays or prevents the occurrence of spontaneous seizures. Epilepsia 46 (2005) 269-270 (abstract)
38. Francois J., Boehrer A., and Nehlig A. Effects of carisbamate (RWJ-333369) in two models of genetically determined generalized epilepsy, the GAERS and the audiogenic Wistar AS. Epilepsia 49 (2008) 393-399
39. French J.A., Brodsky A., von Rosenstiel P., and on behalf of the Brivaracetam N01193 Study Group. Efficacy and tolerability of 5, 20 and 50 mg/day brivaracetam (UCB 34714) as adjunctive treatment in adults with refractory partial-onset seizures. Epilepsia 48 Suppl. 6 (2007) 400
40. Funk A.P., Ricci R., Anderson B.A., Arana A.B., De Colle C., Wang S., and George M.S. Single doses of JZP-4 decrease cortical excitability. A transcranial magnetic stimulation study. American Epilepsy Society 2008 Annual Meeting (2008)
41. Ganes, D., Moros, D., Levitt, B., Rutman, H., LeBel, M., Yacobi, A., 2006. Safety and pharmacokinetics of T2000, a novel non-sedating barbiturate, after multiple oral doses in healthy subjects. American Association of Pharmaceutical Scientists Annual Meeting and Exposition, October 29-November 2, San Antonio, TX (www.aapsj.org/abstracts/AM_2006/AAPS2006-003327.pdf).
42. Garriga-Canut M., Schoenike B., Qazi R., Bergendahl K., Daley T.J., Pfender R., Morrison J.F., Ockuly J., Stafstrom C., Sutula T., and Roopra A. 2-Deoxy-d-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Nat. Neurosci. 9 (2006) 1382-1387
43. Grabenstatter H., and Dudek F. The use of chronic models in antiepileptic drug discovery: the effect of RJW-333369 on spontaneous motor seizures in rats with kainite-induced epilepsy. Epilepsia 45 (2004) 197 (abstract)
44. Grabenstatter, H.L., Dudek, F.E., 2008. A new potential AED, carisbamate, substantially reduces spontaneous motor seizures in rats with kainate-induced epilepsy. Epilepsia, 2008 May 20 [Epub ahead of print].
45. Halasz P., Kalviainen R., Mazurkiewicz-Beldzinska M., Rosenow F., Doty P., and Suillvan T. Lacosamide: efficacy and safety as oral adjunctive therapy in adults with partial seizures. Epilepsia 47 Suppl. 4 (2006) 3 (abstract)
46. Hansen I.L., Levy M.M., and Kerr D.S. The 2-deoxyglucose test as a supplement to fasting for detection of childhood hypoglycemia. Ped. Res. 18 (1984) 359-364
47. He X.P., Kotloski R., Nef S., Luikart B., Parada L.F., and McNamara J.O. Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model. Neuron 43 (2004) 31-42
48. A receptors. Pharmacol. Ther. 116 (2007) 20-34
49. Herdon H.J., Jerman J.C., Stean T.O., Middlemiss D.N., Chan W.N., Vong A.K., Evans J.M., Thompson M., and Upton N. Characterization of the binding of [3H]-SB-204269, a radiolabelled form of the new anticonvulsant SB-204269, to a novel binding site in rat brain membranes. Br. J. Pharmacol. 121 (1997) 1687-1691
50. Hetka R., Rundfeldt C., Heinemann U., and Schmitz D. Retigabine strongly reduces repetitive firing in rat entorhinal cortex. Eur. J. Pharmacol. 386 (1999) 165-171
51. Hirano K., Kuratani K., Fujiyoshi M., Tashiro N., Hayashi E., and Kinoshita M. Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci. Lett. 413 (2007) 159-162
52. Horstmann R., Bonn R., Cawello W., Doty P., and Rudd D. Basic clinical pharmacological investigations of the new antiepileptic drug SPM 927. Epilepsia 43 Suppl. 7 (2002) 188 (Abstract 2.174)
53. A receptors through two discrete transmembrane sites. Nature 444 (2006) 486-489
54. Hovinga C.A. SPM-927 (schwarz pharma). Drugs 6 (2003) 479-485
55. Huguenard J.R., and Wilson W.A. Suppression of repetitive firing of neurons by diphenylbarbituric acid. J. Pharmacol. Exp. Ther. 232 (1985) 228-231
56. Isoherranen N., Woodhead J.H., White H.S., and Bialer M. Anticonvulsant profile of valrocemide (TV1901): a new antiepileptic drug. Epilepsia 42 (2001) 831-836
57. Isoherranen N., Yagen B., Woodhead J.H., Spiegelstein O., Blotnik S., Wilcox K.S., Finnell R.H., Bennett G.D., White H.S., and Bialer M. Characterization of the anticonvulsant profile and enantioselective pharmacokinetics of the chiral valproylamide propylisopropyl acetamide in rodents. Br. J. Pharmacol. 138 (2003) 602-613
58. Kaminski R.M., Gasior M., Carter R.B., and Wilkin J.M. Protective efficacy of neuroactive steroids against cocaine kindled-seizures in mice. Eur. J. Pharmacol. 474 (2003) 217-222
59. Kaminski R.M., Livingood M.R., and Rogawski M.A. Allopregnanolone analogs that positively modulate GABA receptors protect against partial seizures induced by 6-Hz electrical stimulation in mice. Epilepsia 45 (2004) 864-867
60. Kaminski R.M., Matagne A., Leclercq K., Gillard M., Michel P., Kenda B., Talaga P., and Klitgaard H. SV2A protein is a broad-spectrum anticonvulsant target: functional correlation between protein binding and seizure protection in models of both partial and generalized epilepsy. Neuropharmacology 54 (2008) 715-720
61. Kasteleijn-Nolst Trenité D.G., Genton P., Parain D., Masnou P., Steinhoff B.J., Jacobs T., Pigeolet E., Stockis A., and Hirsch E. Evaluation of brivaracetam, a novel SV2A ligand, in the photosensitivity model. Neurology 69 (2007) 1027-1034
62. Kasteleijn-Nolst Trenité D.G.A., Biton V., Wang S., De Colle C., and Isojarvi J. Evidence of activity for JZP-4, a novel sodium and calcium channel inhibitor in photosensitive epilepsy patients, an exploratory study. American Epilepsy Society 2008 Annual Meeting (2008)
63. Kaufmann D., Yagen B., Minert A., Tal M., Devor M., and Bialer M. Evaluation of the enantioselective antiallodynic profile and pharmacokinetics of propylisopropylacetamide, a chiral isomer of valproic acid amide. Neuropharmacology 54 (2008) 699-707
64. Kerrigan J.F., Shields W.D., Nelson T.Y., Bluestone D.L., Dodson W.E., Bourgeois B.F., Pellock J.M., Morton L.D., and Monaghan E.P. Ganaxolone for treating intractable infantile spasms: a multicenter, open-label, add-on trial. Epilepsy Res. 42 (2000) 133-139
65. Kinney G.A., Emmerson P.J., and Miller R.J. Galanin receptor-mediated inhibition of glutamate release in the arcuate nucleus of the hypothalamus. J. Neurosci. 18 (1998) 3489-3500
66. Klein B., Smith M.D., and White H.S. The novel neuromodulator carisbamate delays the acquisition of rat amygdala kindling and maintains acute antiepileptic activity when evaluated in post-kindled rats. Presented at: the 61st Annual Meeting of the American Epilepsy Society. Philadelphia, PA, USA, November 30-December 4 (2007)
67. Matagne A., and Klitgaard H. Validation of corneally kindled mice: a sensitive screening model for partial epilepsy in man. Epilepsy Res. 31 (1998) 59-71
68. Knoefel P.K., and Lehmann G. The anticonvulsant action of diphenylhydantoin and some related compounds. J. Pharmacol. Exp. Ther. 76 (1942) 194-201
69. Korsgaard M.P., Hartz B.P., Brown W.D., Ahring P.K., Strøbaek D., and Mirza N.R. Anxiolytic effects of Maxipost (BMS-204352) and retigabine via activation of neuronal Kv7 channels. J. Pharmacol. Exp. Ther. 314 (2005) 282-292
70. Kropeit D., Schiltmeyer B., Cawello W., Hammes W., and Horstmann R. Bioequivalence of short-time infusions compared to oral administration of SPM 927. Epilepsia 45 Suppl. 7 (2004) 123 (Abstract 1.323)
71. Lacroix B., von Rosenstiel P., and Sargentini-Maier M.L. Population pharmacokinetics of brivaracetam in patients with partial epilepsy. Epilepsia 48 Suppl. 6 (2007) 333
72. Laveille C., Lacroix B., Snoeck E., Sargentini-Maier M.L., von Rosenstiel P., and Stockis A. Dose- and exposure-response modeling of brivaracetam add-on treatment in patients with partial epilepsy. Epilepsia 48 Suppl. 6 (2007) 328
73. Lawrence J.J., Goldschen M., Jones M., Rogawski M.A., and McBain C.J. The Kv7/KCNQ/M channel opener ICA-027243 arrests interneuronal firing and reduces interneuronal network synchrony in the hippocampus: novel insights into the antiepileptic action of Kv7 channel openers. Epilepsia 48 Suppl. 6 (2007) 361 (Abstract 3.307)
74. Laxer K., Blum D., Abou-Khalil B.W., Morrell M.J., Lee D.A., Data J.L., Monaghan E.P., and the Ganaxolone Presurgical Study Group. Assessment of ganaxolone's anticonvulsant activity using a randomized, double-blind, presurgical trial design. Epilepsia 41 (2000) 1187-1194
75. Leśkiewicz M., Budziszewska B., Jaworska-Feil L., Kubera M., Basta-Kaim, and Lason W. Inhibitory effect of some neuroactive steroids on cocaine-induced kindling in mice. Polish J. Pharmacol. 55 (2003) 1131-1136
76. Lian X.Y., Khan F.A., and Stringer J.L. Fructose-1,6-bisphosphate has anticonvulsant activity in models of acute seizures in adult rats. J. Neurosci. 27 (2007) 12007-12011
77. Maia J., Almeida L., Falcão A., Soares E., Mota F., Potgieter J.H., Potgieter M.A., and Soares-da-Silva P. Effect of renal impairment on the pharmacokinetics of eslicarbazepine acetate. Int. J. Clin. Pharmacol. Ther. 46 (2008) 119-130
78. Main M.J., Cryan J.E., Dupere J.R.B., Cox B., Clare J.J., and Burbidge S.A. Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Mol. Pharmacol. 58 (2000) 253-262
79. Mannens G.S., Hendrickx J., Janssen C.G., Chien S., Van H.B., Verhaeghe T., Kao M., Kelley M.F., Goris I., Bockx M., Verreet B., Bialer M., and Meuldermans W. The absorption, metabolism, and excretion of the novel neuromodulator RWJ-333369 (1,2-ethanediol, [1-2-chlorophenyl]-,2-carbamate, [S]-) in humans. Drug Metab. Dispos. 35 (2007) 554-565
80. Marson A.G., Al-Kharusi A.M., Alwaidh M., Appleton R., Baker G.A., Chadwick D.W., Cramp C., Cockerell O.C., Cooper P.N., Droughty J., Eaton B., Gamble C., Coulding P.J., Howell S.J.L., Hughes A., Jackson M., Jacoby A., Kellett M., Lawson G.R., Leach J.P., Nicolaides P., Roberts R., Shackley P., Shen J., Smith D.F., Smith P.E.M., Tudur Smith C., Vanoli A., Williamson P., and on behalf of the SANAD Study Group. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for treatment of generalized and unclassifiable epilepsy: an unblinded randomized controlled trial. Lancet 369 (2007) 1016-1026
81. Matagne A., Margineanu D.-G., Kenda B., Michel P., and Klitgaard H. Anticonvulsive and antiepileptic properties of brivaracetam (ucb 34714), a high affinity synaptic vesicle protein SV2A ligand. Br. J. Pharmacol. 154 (2008) 1662-1671
82. Mazarati A., and Lu X. Regulation of limbic status epilepticus by hippocampal galanin type 1 and type 2 receptors. Neuropeptides 39 (2005) 277-280
83. Mazarati A.M., Halászi E., and Telegdy G. Anticonvulsive effects of galanin administered into the central nervous system upon the picrotoxin-kindled seizure syndrome in rats. Brain Res. 589 (1992) 164-166
84. Mazarati A.M., Liu H., Soomets U., Sankar R., Shin D., Katsumori H., Langel U., and Wasterlain C.G. Galanin modulation of seizures and seizure modulation of hippocampal galanin in animal models of status epilepticus. J. Neurosci. 18 (1998) 10070-10077
85. Mazarati A., Langel U., and Bartfai T. Galanin: an endogenous anticonvulsant?. Neuroscientist 7 (2001) 506-517
86. Mazarati A., Lundström L., Sollenberg U., Shin D., Langel U., and Sankar R. Regulation of kindling epileptogenesis by hippocampal galanin type 1 and type 2 receptors: the effects of subtype-selective agonists and the role of G-protein-mediated signalling. J. Pharmacol. Exp. Ther. 318 (2006) 700-708
87. McElvain S.M. 5,5-Diphenylbarbituric acid. J. Am. Chem. Soc. 57 (1935) 1303-1304
88. McKay, G., Hawes, E.M., Hogge, L., Peng, P., Ganes, D., Yacobi, A., 2006a. Identification of the metabolites of T2000, a novel non-sedating barbiturate, in human. American Association of Pharmaceutical Scientists Annual Meeting and Exposition, October 29-November 2, San Antonio, TX (www.aapsj.org/abstracts/AM_2006/AAPS2006-001703.pdf).
89. McKay, G., Hawes, E.M., Hogge, L., Peng, P., Ganes, D., Yacobi, A., 2006b. Metabolism of T2000, a novel non-sedating barbiturate, in rat and dog. American Association of Pharmaceutical Scientists Annual Meeting and Exposition, October 29-November 2, San Antonio, TX (www.aapsj.org/abstracts/AM_2006/AAPS2006-003495.pdf).
90. Melmed C., Moros D., and Rutman H. Treatment of essential tremor with the barbiturate T2000 (1,3-dimethoxymethyl-5,5-diphenyl-barbituric acid). Movement Disord. 22 (2007) 723-727
91. Merritt H.H., and Putnam T.J. A new series of anticonvulsant drugs tested by experiments on animals. Arch. Neurol. Psychiatry 39 (1938) 1003-1015
92. Merritt H.H., and Putnam T.J. Experimental determination of anticonvulsive activity of chemical compounds. Epilepsia 3 (1945) 51-75
93. Monaghan E.P., Navalta L.A., Shum L., Ashbrook D.W., and Lee D.A. Initial human experience with ganaxolone, a neuroactive steroid with antiepileptic activity. Epilepsia 38 (1997) 1026-1031
94. Moore K.T., Zannikos P., Solanki B., Greenspan A., Romano G., and Brashear H.R. Single-dose pharmacokinetics of carisbamate in subjects with normal and impaired hepatic function. Clin. Pharmacol. Ther. 83 Suppl. 1 (2008) S24
95. Moros D., and Rutman H. T2000 A non-sedating barbiturate with antiepileptic activity under study in essential tremor. Antiepileptic Drug Trials IX Syllabus. Sunny Isles Beach, FL, USA, March 21-24 (2007)
96. Munro G., Erichsen H.K., and Mirza N.R. Pharmacological comparison of anticonvulsant drugs in animal models of persistent pain and anxiety. Neuropharmacology 53 (2007) 609-618
97. Newman G., Hospod F., and Patlak C. Kinetic model of 2-deoxyglucose metabolism using brain slices. J. Cereb. Blood. Flow Metab. 10 (1990) 510-526
98. Nguyen, L., Tao, L., Nash, J., Peng, P., Ganes, D., Yacobi, A., 2006. Evaluation of the potential for drug-drug interactions of T2000 and its major metabolites in human liver microsomes and primary human hepatocytes in culture. American Association of Pharmaceutical Scientists Annual Meeting and Exposition, October 29-November 2, San Antonio, TX (www.aapsj.org/abstracts/AM_2006/AAPS2006-002694.pdf).
99. Nguyen, L., Gagnon, S., Erlemann, K.-R., Tao, L., Nash, J., Peng, P., Ganes, D., Yacobi, A., 2007. Induction of cytochromes P450 in Sprague-Dawley rats and Beagle dogs following dosing with T2000 and comparison to the inductive response in primary human hepatocytes. American Association of Pharmaceutical Scientists Annual Meeting and Exposition, November 11-15, 2007, San Diego, CA (www.aapsj.org/abstracts/AM_2007/AAPS2007-001507.pdf).
100. Nielsen A.N., Mathiesen C., and Blackburn-Munro G. Pharmacological characterisation of acid-induced muscle allodynia in rats. Eur. J. Pharmacol. 487 (2004) 93-103
101. Nohria V., and Giller E. Ganaxolone. Neurotherapeutics 4 (2007) 102-105
102. Otoul C., von Rosenstiel P., and Stockis A. Evaluation of the pharmacokinetic interaction of brivaracetam on other antiepileptic drugs in adults with partial-onset seizures. Epilepsia 48 Suppl. 6 (2007) 334
103. Otto J.F., Kimball M.M., and Wilcox K.S. Effects of the anticonvulsant retigabine on cultured cortical neurons: changes in electroresponsive properties and synaptic transmission. Mol. Pharmacol. 61 (2002) 921-927
104. Parada A., and Soares-da-Silva P. The novel anticonvu comparison with carbamazepine and oxcarbazepine. Neurochem. Int. 40 (2002) 435-440
105. Parada A., and Soares-da-Silva P. Lsant BIA 2-093 inhibits transmitter release during opening of voltage-gated sodium channels: a comparison with carbamazepine and oxcarbazepine. Nurochem. Int. 40 (2002) 435-440
106. Parsons A.A., Bingham S., Raval P., Read S., Thompson M., and Upton N. Tonabersat (SB-220453) a novel benzopyran with anticonvulsant properties attenuates trigeminal nerve-induced neurovascular reflexes. Br. J. Pharmacol. 132 (2001) 1549-1557
107. Pieribone V.A., Tsai J., Soufflet C., Rey E., Shaw K., Giller E., and Dulac O. Clinical evaluation of ganaxolone in pediatric and adolescent patients with refractory epilepsy. Epilepsia 48 (2007) 1870-1874
108. Porter R.J., Partiot A., Sachdeo R., Nohria V., and Alves W.M. Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures. Neurology 68 (2007) 1197-1204
109. Raez L.E., Langmuir V., Tolba K., Rocha-Lima C.M., Papadopoulos K., Kroll S., Brawer M., Rosenblatt J., Ricart A., and Lampidis T. Responses to the combination of the glycolytic inhibitor 2-deoxy-glucose (2DG) and docetaxel (DC) in patients with lung and head and neck (H/N) carcinomas. ASCO Annual Meeting Proceedings. J. Clin. Onc. 25 18S (2007) 14025
110. Raines A., Niner J.M., and Pace D.G. A comparison of the anticonvulsant, neurotoxic and lethal effects of diphenylbarbituric acid, phenobarbital and diphenylhydantoin in the mouse. J. Pharmacol. Exp. Ther. 186 (1973) 315-322
111. Raines A., Baumel I., Gallagher B.B., and Niner J.M. The effects of 5,5-diphenylbarbituric acid on experimental seizures in rats: correlation between plasma and brain concentrations and anticonvulsant activity. Epilepsia 16 (1975) 575-581
112. Raines A., Ganes D., Levitt B., Moros D., LeBel M., Rutman H., and Yacobi A. Enhancement by a high fat meal of the absorption of orally administered T2000 (1,3-bismethoxymethyl-5,5-diphenylbarbituric acid; I) in man. Experimental Biology. Washington, DC, April 28-May 2. FASEB J. 21 (2007) 566.2
113. Read S.J., Smith M.I., Hunter A.J., Upton A.J., and Parsons A.A. SB-220453, a potential novel antimigraine agent, inhibits nitric oxide release following induction of cortical spreading depression in the anaesthetised cat. Cephalalgia 20 (2000) 92-99
114. Read S.J., Hirst W.D., Upton N., and Parsons A.A. Cortical spreading depression produces increased cGMP levels in cortex and brain stem that is inhibited by tonabersat (SB-220453) but not sumatriptan. Brain Res. 891 (2001) 69-77
115. Reddy D.S., and Rogawski M.A. Chronic treatment with the neuroactive steroid ganaxolone in the rat induces anticonvulsant tolerance to diazepam but not to itself. J. Pharmacol. Exp. Ther. 295 (2000) 1241-1248
116. Richter A., Tober C., and Rundfeldt C. Antidystonic effects of Kv7 (KCNQ) channel openers in the dt sz mutant, an animal model of primary paroxysmal dystonia. Br. J. Pharmacol. 149 (2006) 747-753
117. Rogawski M.A., and Reddy D.S. Neurosteroids: endogenous modulators of seizure susceptibility. In: Rho J.M., Sankar R., and Cavazos J. (Eds). Epilepsy: Scientific Foundations of Clinical Practice (2004), Marcel Dekker, New York 319-355
118. Rolan P., Sargentini-Maier M.L., Pigeolet E., and Stockis A. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after multiple increasing oral doses in healthy males. Br. J. Clin. Pharmacol. 66 (2008) 71-75
119. Rosillon D., Astruc B., Hulhoven R., Meeus M.A., Troenaru M.M., Watanabe S., and Stockis A. Effect of brivaracetam on cardiac repolarisation-a thorough QT study. Curr. Med. Res. Opin. 24 (2008) 2327-2337
120. Rostock A., Tober C., Rundfeldt C., Bartsch R., Engel J., Polymeropoulos E., Kutscher B., Loscher W., Honack D., White H.S., and Wolf H.H. D-23129: a new anticonvulsant with a broad spectrum activity in animal models of epileptic seizures. Epilepsy Res. 23 (1996) 211-223
121. Rundfeldt C., and Netzer R. The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells transected with human KDNQ2/3 subunits. Neurosci. Lett. 281 (2000) 73-76
122. Sander S.E., and Richter A. Antidyskinetic effects of the KV7 channel opener retigabine in an animal model of levodopa-induced dyskinesia. Göttingen Meeting of the German Neuroscience Society Göttingen. Germany (2007) T35-4A
123. Sargentini-Maier M.L., Rolan P., Connell J., Tytgat D., Jacobs T., Pigeolet E., Riethuisen J.M., and Stockis A. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after single increasing oral doses in healthy males. Br. J. Clin. Pharmacol. 63 (2007) 680-688
124. Sargentini-Maier M.L., Espié P., Coquette A., and Stockis A. Pharmacokinetics and metabolism of 14C-brivaracetam, a novel SV2A ligand, in healthy subjects. Drug Metab. Dispos. 36 (2008) 36-45
125. Schachter, S., White H.S., Murphree L., Stables, J., 2006. Anticonvulsant activity of Huperzine A, an alkaloid extract of Chinese club moss (Huperzia serrata), in the 6-Hz model of psychomotor seizures. http://www.aesnet.org/go/publications/aes-abstracts/abstractsearch/?mode =display&st=Schachter&sy=2006&sb=All&startrow=1&id=6 996. Abstract 4.087.
126. Schiltmeyer B., Cawello W., Kropeit D., Hammes W., and Horstmann R. Pharmacokinetics of the new antiepileptic drug SPM 927 in human subjects with different age and gender. Epilepsia 45 Suppl. 7 (2004) 313 (Abstract 2.361)
127. Shimshoni J., Dalton E.C., Jenkins E., Eyal S., Ewen K., Williams R.S.B., Pessah N., Yagen B., Harwood J.A., and Bialer M. The effect of CNS-active valproic acid constitutional isomers, cyclopropyl analogues and amide derivatives on neuronal growth cone behavior. Mol. Pharmacol. 71 (2007) 884-892
128. Sokoloff L., Reivich M., Kennedy C., Des Rosiers M.H., Patlak C.S., Pettigrew K.D., Sakurada O., and Shinohara M. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J. Neurochem. 28 (1977) 897-916
129. Spiegelstein O., Yagen B., Levy R.H., Finnell R.H., Bennett G.D., Roeder M., Schurig V., and Bialer M. Stereoselective pharmacokinetics and pharmacodynamics of propylisopropyl acetamide, a CNS-active chiral amide analog of valproic acid. Pharm. Res. 16 (1999) 1582-1588
130. Srivastava A.K., and White H.S. Retigabine decreases behavioral and electrographic seizures in the lamotrigine-resistant amygdal kindled rat model of pharmacoresistant epilepsy. Epilepsia 46 Suppl. 8 (2005) 217 (Abstract 2.375)
131. Stafstrom, C.E., Ockuly, J.C, Murphree, L., Valley, M.T., Roopra, A., Sutula, T.P. Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models. Submitted for publication.
132. Stoehr T., Kupferberg H.J., Stables J.P., Choi D., Harris R.H., Kohn H., Walton N., and White H.S. Lacosamide, a novel anticonvulsant drug, shows efficacy with a wide safety margin in rodent models for epilepsy. Epilepsy Res. 74 (2007) 147-154
133. Tatulian L., and Brown D.A. Effect of the KCNQ potassium channel opener retigabine on single KCNQ2/3 channels expressed in CHO cells. J. Physiol. 549 (2003) 57-63
134. Tatulian L., Delmas P., Abogadie F.C., and Brown D.A. Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine. J. Neurosci. 21 (2001) 5535-5545
135. Thomas D., Scharfenecker U., Schiltmeyer B., et al. Low potential for drug-drug interaction of lacosamide. Epilepsia 47 Suppl. 4 (2006) 200 (abstract)
136. Tober C., Rostock A., Rundfeldt C., and Bartsch R. D-23129 a potent anticonvulsant in the amygdala kindling model of complex partial seizures. Eur. J. Pharmacol. 303 (1996) 163-169
137. Thomas D., Scharfenecker U., Schiltmeyer B., Cawello W., Doty P., and Horstmann R. Low potential for drug-drug interaction of lacosamide. Epilepsia 47 Suppl. 4 (2006) 200 (abstract)
138. Tremblay, P., Shink, E., Abolfathi, Z., Tanguay, M., Lebel, M., Peng, P., Ganes, D., Yacobi, A., 2006. Pharmacokinetic modeling of the novel non-sedating barbiturate T2000 and its active metabolites in plasma and urine. American Association of Pharmaceutical Scientists Annual Meeting and Exposition, October 29-November 2, San Antonio, TX (www.aapsj.org/abstracts/AM_2006/AAPS2006-003092.pdf).
139. Upton N., Raval P., Herdon H., Jerman J., and Parsons A.A. SB-220453, a mechanistically novel benzopyran compound, inhibits trigeminal nerve ganglion (TGN) stimulation-induced carotid vasodilation. Cephalalgia 19 (1999) 351
140. van Paesschen W., Brodsky A., and on behalf of the Brivaracetam N01114
141. Ward J., and Caprio V. A radical mediated approach to the core structure of Huperzine A. Tetrahedron Lett. 47 (2006) 553-556
142. Wasterlain C., Suchomelova L., Matagne A., Klitgaard H., Mazarati A., Shinmei S., and Baldwin R. Brivaracetam is a potent anticonvulsant in experimental status epilepticus. Epilepsia 46 Suppl. 8 (2005) 219
143. White H.S., Schachter S., Lee D., Xiaoshen J., and Eisenberg D. Anticonvulsant activity of Huperzine A, an alkaloid extract of Chinese club moss (Huperzia serrata). Epilepsia 46 Suppl. 8 (2005) 220
144. White H., Srivastava A., Klein B., et al. The novel investigational neuromodulator RWJ-333369 displays a broad-spectrum anticonvulsant profile in rodent seizure and epilepsy models (abstract). Epilepsia 27 (2006) 200
145. Wuttke T.V., Seebohm G., Bail S., Maljevic S., and Lerche H. The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. Mol. Pharmacol. 67 (2005) 1009-1017
146. Xu T., and Bajjalieh S.M. SV2 modulates the size of the readily releasable pool of secretary vesicles. Nat. Cell Biol. 3 (2001) 691-698
147. Yacobi, A., Ganes, D., Callozzo, J., Lai, C., Peng, P, 2006. Examination of in vitro protein binding of T2000, a novel non-sedating barbiturate, in mouse, rat, rabbit, dog and human plasma. American Association of Pharmaceutical Scientists Annual Meeting and Exposition, October 29-November 2, San Antonio, TX (www.aapsj.org/abstracts/AM_2006/AAPS2006-003222.pdf).
148. Yao C., Doose D.R., Novak G., and Bialer M. Pharmacokinetics of the new antiepileptic and CNS drug RWJ-333369 following single and multiple dosing to humans. Epilepsia 47 (2006) 1822-1829
149. Zangara A. The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer's disease. Pharmacol. Biochem. Behav. 75 (2003) 675-686
150. Zavadil III A.P., Dretchen K.L., and Raines A. Diphenylbarbituric acid: its effects on neuromuscular and spinal cord function in the cat. Epilepsia 26 (1985) 158-166