New and investigational antiepileptic drugs

Expert Opinion on Investigational Drugs

Volumn 18, Issue 12, 2009, Pages 1875-1884

  Striano, Pasquale ^a   Striano, Salvatore ^b  

^a G GASLINI INSTITUTE   (Italy)

^b UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

Antiepileptic drugs; Drug discovery; Epilepsy; New drugs; Therapy

Indexed keywords

1,3 DIMETOXYMETHYL 5,5 DIPHENYLBARBITURIC ACID; 3 (2,3,5 TRICHLORO PHENYL)PYRAZINE 2,6 DIAMINE; 3,3 DIMETHYLBUTANOYLUREA; 5,5 DIPHENYLBARBITURIC ACID; ANTICONVULSIVE AGENT; AR 12495AA; BARBITURIC ACID DERIVATIVE; BRIVARACETAM; CARISBAMATE; DICARBAMATE FELBAMATE; DIISOPROPYL ACETAMIDE; ESLICARBAZEPINE ACETATE; ETEROBARB; ETIRACETAM; F 12495AA; FLUOROFELBAMATE; FPL 12925; JZP 4; LICARBAZEPINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; PHENOBARBITAL; PLACEBO; PRIMIDONE; REMACEMIDE; SELETRACETAM; T 2000; TALAMPANEL; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALNOCTAMIDE; VALPROIC ACID; VALPROMIDE; VALROCEMIDE;

ADD ON THERAPY; ANTICONVULSANT ACTIVITY; BIPOLAR DISORDER; BLOOD TOXICITY; CLINICAL TRIAL; CLONIC SEIZURE; COMPLEX PARTIAL SEIZURE; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; EPILEPSY; EPILEPTIC STATE; ESSENTIAL TREMOR; FOCAL EPILEPSY; GAP JUNCTION; GRAND MAL SEIZURE; HUMAN; LIVER TOXICITY; MYOCLONUS DYSTONIA; NONHUMAN; RECURRENT DISEASE; REVIEW; SEIZURE; SKIN MANIFESTATION; TERATOGENICITY; UNSPECIFIED SIDE EFFECT;

AMINO ACIDS; ANTICONVULSANTS; DRUG DELIVERY SYSTEMS; DRUGS, INVESTIGATIONAL; EPILEPSY; HUMANS; KETOGENIC DIET; NEUROTRANSMITTER AGENTS; STEREOISOMERISM;

EID: 72249088842     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543780903369341     Document Type: Review

References (98)

1. Shorvon SD. Drug treatment of epilepsy in the century of the ILAE: the second 50 years, 1959-2009. Epilepsia 2009;50(Suppl 3):93-130
2. Johannessen Landmark C, Johannessen SI. Pharmacological management of epilepsy: recent advances and future prospects. Drugs 2008;68:1925-39
3. Ben-Menachem E. Strategy for utilization of new antiepileptic drugs. Curr Opin Neurol 2008;21:167-172
4. Schmidt D, Loscher W. Drug-resistance in epilepsy: putative neurobiologic and clinical mechanisms. Epilepsia 2005;46:858-877
5. Duncan S. Teratogenesis of sodium valproate. Curr Opin Neurol 2007;20:175-180
6. Rogawski MA. Diverse mechanisms of antiepileptic drugs in the development pipeline. Epilepsy Res 2006;69:273-294
7. Bialer M. New antiepileptic drugs that are second generation to existing antiepileptic drugs. Expert Opin Investig Drugs 2006;15:637-647
8. Almeida L, Falcao A, Maia J, et al. Single-dose and steady-state pharmacokinetics of eslicarbazepine acetate (BIA 2-093) in healthy elderly and young subjects. J Clin Pharmacol 2005;45:1062-1066
9. Almeida L, Soares-da-Silva P. Eslicarbazepine acetate (BIA 2-093). Neurotherapeutics 2007;4:88-96
10. Parada A, Soares-da-Silva P. The novel anticonvulsant BIA 2-093 inhibits transmitter release during opening of voltage-gated sodium channels: a comparison with carbamazepine and oxcarbazepine. Neurochem Int 2002;40:435-440
11. Elger C, Halàsz P, Maia J, et al. Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures: a randomized, double-blind, placebo-controlled, parallel-group phase 3 study. Epilepsia 2009;50:454-463
12. McCormack PL, Robinson DM. Eslicarbazepine acetate. CNS Drugs 2009;23:71-79
13. Elger C, Halász P, Maia J, et al; BIA-2093-2301
14. Investigators Study Group. Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures: a randomized, double-blind, placebo-controlled, parallel-group phase III study. Epilepsia 2009:50:454-463
15. Kenda BM, Matagne AC, Talaga PE, et al. Discovery of 4-substituted pyrrolidone butanamides as new agents with significant antiepileptic activity. J Med Chem 2004;47:530-549
16. Lynch BA, Lambeng N, Nocka K, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci USA 2004;101:9861-9866
17. Matagne A, Margineanu DG, Kenda B, et al. Anticonvulsive and antiepileptic properties of brivaracetam (ucb 34714), a high affinity synaptic vesicle protein SV2A ligand. Br J Pharmacol 2008;154:1662-1671
18. Kaminski RM, Matagne A, Leclercq K, et al. 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 2008;54:715-720
19. Martella G, Bonsi P, Sciamanna G, et al. Seletracetam (ucb 44212) inhibits high-voltage-activated Ca2+ currents and intracellular Ca2+ increase in rat cortical neurons in vitro. Epilepsia 2009;50:702-710
20. Sargentini-Maier ML, Rolan P, Connell J, et al. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after single increasing oral doses in healthy males. Br J Clin Pharmacol 2007;63:680-688
21. Klitgaard H. Levetiracetam: the preclinical profile of a new class of antiepileptic drugs? Epilepsia 1992;42(Suppl 4):13-18
22. French JA, Brodsky A, von Rosenstiel P; on behalf of the Brivaracetam N01193
23. 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 2007;48(Suppl 6):400
24. Laveille C, Lacroix B, Snoeck E, et al. Dose-and exposure-response modeling of brivaracetam add-on treatment in patients with partial epilepsy. Epilepsia 2007;48(Suppl 6):328
25. Pollard JR. Seletracetam, a small molecule SV2A modulator for the treatment of epilepsy. Curr Opin Investig Drugs 2008;9:101-7
26. Thompson CD, Miller TA, Barthen MT, et al. The synthesis, in vitro reactivity, and evidence for formation in humans of 5-phenyl-1,3-oxazinane-2,4- dione, a metabolite of felbamate. Drug Metab Dispos 2000;28:434-439
27. Bialer M, Johannessen SI, Levy RH, et al. Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX). Epilepsy Res 2009;83:1-43
28. Grabenstatter HL, Dudek FE. A new potential AED, carisbamate, substantially reduces spontaneous motor seizures in rats with kainate-induced epilepsy. Epilepsia 2008;49:1787-1794
29. Francois J, Boeher A, Nehlig A. Effects of carisbamate (RWJ-333369) in two models of genetically determined generalized epilepsy, the GAERS and the audiogenic Wistar AS. Epilepsia 2008;49:393-399
30. Nehlig A, Rigoulot MA, Boehrer A. A new drug, RWJ 333369 displays potent antiepileptic properties in genetic models of absence and audiogenic epilepsy. Epilepsia 2005;46(Suppl 8):215
31. Francois J, Ferrandon A, Koning E, Nehlig A. A new drug RWJ 333369 protects limbic areas in the lithium-pilocarpine model (li-pilo) of epilepsy and delays or prevents the occurrence of spontaneous seizures Epilepsia 2005;46(Suppl 8):269-270
32. Chien S, Bialer M, Solanki B, et al. Pharmacokinetic interaction study between the new antiepileptic and CNS drug RWJ-333369 and carbamazepine in healthy adults. Epilepsia 2006;47:1830-1840
33. Faught E, Holmes GL, Rosenfeld WE, et al. Randomized, controlled, dose-ranging trial of carisbamate for partial-onset seizures. Neurology 2008;71:1586-1593
34. Radatz M, Ehlers K, Yagen B, et al. Valnoctamide, valpromide and valnoctic acid are much less teratogenic in mice than valproic acid. Epilepsy Res 1998;30:41-48
35. Winkler I, Blotnik S, Shimshoni J, et al. Efficacy of antiepileptic isomers of valproic acid and valpromide in a rat model of neuropathic pain. Br J Pharmacol 2005;146:198-208 (Pubitemid 43079959)
36. Isoherranen N, Woodhead JH, White HS, Bialer M. Anticonvulsant profile of valrocemide (TV1901). Epilepsia 2001;42:832-6
37. Funk AP, Ricci R, Anderson BA, et al. Single doses of JZP-4 decrease cortical excitability. A transcranial magnetic stimulation study. American Epilepsy Society. Epilepsia 2008;49(Suppl 7):431 [abstract] Kasteleijn-Nolst
38. Trenité D, Rosenfeld W, Wang S, et al. Evidence of activity for JZP-4, a novel sodium calcium channel inhibitor in photosensitive epilepsy patients: an exploratory study. American Epilepsy Society Congress. Epilepsia 2008;49(Suppl 7):439 [abstract 3.221]
39. McKay G, Hawes EM, Hogge L, et al. Metabolism of T2000, a novel non-sedating barbiturate, in rat and dog. American Association of Pharmaceutical Scientists Annual Meeting and Exposition 2006, 29 October-2 November, San Antonio, TX, USA. Available from: www.aapsj.org/abstracts/AM-2006/AAPS2006- 003495.pdf [Last access 26 October 2009]
40. McKay G, Hawes EM, Hogge L, et al. Identification of the metabolites of T2000, a novel non-sedating barbiturate, in human. American Association of Pharmaceutical Scientists Annual Meeting and Exposition 2006, 29 October-2 November, San Antonio, TX, USA Available from: www.aapsj.org/abstracts/AM-2006/ AAPS2006-001703.pdf [Last access 26 October 2009]
41. Davies JA. Remacemide hydrochloride: a novel antiepileptic agent. Gen Pharmacol 1997;28:499-502
42. Meldrum BS, Rogawsky MA. Molecular targets for antiepileptic drug development. Neurotherapeutics 2007;4:18-61
43. Barton ME, Peters SC, Shannon HE. Comparison of the effect of glutamate receptor modulators in the 6 Hz and maximal electroshock seizure models. Epilepsy Res 2003;56:17-26
44. Takahashi M, Ni JW, Kawasaki-Yatsugi S, et al. YM872, a novel selective alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, reduces brain damage after permanent focal cerebral ischemia in cats. J Pharmacol Exp Ther 1998;284:467-473
45. Turski L, Huth A, Sheardown M, et al. ZK200775: a phosphonate quinoxalinedione AMPA antagonist for neuroprotection in stroke and trauma. Proc Natl Acad Sci USA 1998;95:10960-10965
46. Walters MR, Kaste M, Lees KR, et al. The AMPA antagonist ZK 200775 in patients with acute ischaemic stroke: a double-blind, multicentre, placebo-controlled safety and tolerability study. Cerebrovasc Dis 2005;20:304-309
47. Pollard JR, French J. Antiepileptic drugs in development. Lancet Neurol 2006;5:1064-1067
48. Aujla PK, Fetell MR, Jensen FE. Talampanel suppresses the acute and chronic effects of seizures in a rodent neonatal seizure model. Epilepsia 2009;50:694-701
49. Howes JF, Bell C. Talampanel. Neurotherapeutics 2007;4:126-129
50. Langan YM, Lucas R, Jewell H, et al. Talampanel, a new antiepileptic drug: single-and multiple-dose pharmacokinetics and initial 1 week experience in patients with chronic intractable epilepsy. Epilepsia 2003;44:46-53
51. Chappell AS, Sander JW, Brodie MJ, et al. A cross-over, add-on trial of talampanel in patients with refractory partial seizures. Neurology 2002;58:1680-1682
52. Perampanel. Investigator's brochure. 7th edition. Eisai pharma (updated: 19 September 2007)
53. Tatulian L, Brown DA. Effect of the KCNQ potassium channel opener retigabine on single KCNQ2/3 channels expressed in CHO cells. J Physiol 2003;549:57-63
54. Tatulian L, Delmas P, Abogadie FC, Brown DA. Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine. J Neurosci 2001;21:5535-5545
55. Schroeder BC, Kubisch C, Stein V, Jentsch TJ. Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature 1998;396:687-690
56. van Rijn CM, Willems-van Bree E. Synergy between retigabine and GABA in modulating the convulsant site of the GABAA receptor complex. Eur J Pharmacol 2003;464:95-100
57. Blackburn-Munro G, Dalby-Brown W, Mirza NR, et al. Retigabine: chemical synthesis to clinical application. CNS Drug Rev 2005;11:1-20
58. Wickenden AD, Krajewski JL, London B, et al. N-(6-chloro-pyridin-3-yl)-3, 4-difluoro-benzamide (ICA-27243): a novel, selective KCNQ2/Q3 potassium channel activator. Mol Pharmacol 2008;73:977-986
59. Porter RJ, Nohria V, Rundfeldt C. Retigabine. Neurotherapeutics 2007;4:149-154
60. Wickenden AD, McNaughton-Smith G, Roeloffs R, et al. ICA-27243: a novel, potent, and selective KCNQ2/Q3 potassium channel activator. Congress of Neuroscience Societies [abstract 153]
61. McKernan RM, Rosahl TW, Reynolds DS, et al. Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABAA receptor alpha1 subtype. Nat Neurosci 2000;3:587-592
62. Atack JR, Wafford K, Tye SJ, et al. TPA023, an agonist selective for alpha2-and alpha3-containing GABAA receptors, is a non-sedating anxiolytic in rodents and primates. J Pharmacol Exp Ther 2006;316:410-422
63. Chan WN, Evans JM, Hadley MS, et al. Thompson and N. Upton, Identification of (-)-cis-6-acetyl-4S-(3-choro-4-Fluoro-benzoylamino)-3,4- dihydro-2,2-dimethyl-2H-benzo-[b]pyran-3S-ol as a potential antimigraine agent. Bioorg Med Chem Lett 1999;2:285-290
64. Parsons AA, Bingham S, Raval P, et al. Tonabersat (SB-220453) a novel benzopyran with anticonvulsant properties attenuates trigeminal nerve-induced neurovascular reflexes. Br J Pharmacol 2001;132:1549-1557
65. Beyreuther BK, Freitag G, Heers C, et al. Lacosamide: a review of preclinical studies CNS Drug Rev 2007;13:21-42
66. Czech T, Yang JW, Csaszar E, et al. Reduction of hippocampal collapsin response mediated protein-2 in patients with mesial temporal lobe epilepsy. Neurochem Res 2004;29:2189-2196
67. Brandt C, Heile A, Potschka H, et al. Effects of the novel antiepileptic drug lacosamide on the development of amygdala kindling in rats. Epilepsia 2006;47:1803-1809
68. Ben-Menachem E, Biton V, Jatuzis D, et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia 2007;48:1308-1317
69. Halasz P, Kalviainen R, Mazurkiewicz-Beldzinska M, et al. Adjunctive lacosamide for partial-onset seizures: efficacy and safety results from a randomized controlled trial. Epilepsia 2009;50:443-453
70. Hamilton NM. Interaction of steroids with the GABA-A receptor. Curr Top Med Chem 2002;2:887-902
71. Reddy DS, Castaneda DC, O'Malley BW, Rogawski MA. Anticonvulsant activity of progesterone and neurosteroids in progesterone receptor knockout mice. J Pharmacol Exp Ther 2004;310:230-239
72. Reddy DS, Rogawski MA. Chronic treatment with the neuroactive steroid ganaxolone in the rat induces anticonvulsant tolerance to diazepam but not to itself. J Pharmacol Exp Ther 2000;295:1241-1248
73. Reddy DS, Rogawski MA. Enhanced anticonvulsant activity of ganaxolone after neurosteroid withdrawal in a rat model of catamenial epilepsy J Pharmacol Exp Ther 2000;294:909-915
74. Nohria V, Giller E. Ganaxolone. Neurotherapeutics 2007;4:102-105
75. Kerrigan JF, Shields WD, Nelson TY, et al. Ganaxolone for treating intractable infantile spasms: a multicenter, open-label, add-on trial. Epilepsy Res 2000;42:133-139
76. Pieribone VA, Tsai J, Soufflet C, et al. Clinical evaluation of ganaxolone in pediatric and adolescent patients with refractory epilepsy. Epilepsia 2007;48:1870-1874
77. Tuveri A, Paoletti AM, Orrù M, et al. Reduced serum level of THDOC, an anticonvulsant steroid, in women with perimenstrual catamenial epilepsy. Epilepsia 2008;49:1221-1229
78. Bromfield E, Dworetzki B, Hurwitz S, et al. A randomized trial of polyunsaturated fatty acids for refractory epilepsy. Epilepsy Behav 2008;12:187-190
79. Taha AY, Filo E, Ma DWL, McIntyre Burnham W. Dose-dependent anticonvulsant effects of linoleic and alfa-linoleic polyunsaturated fatty acids on pentylentetrazol induced seizures in rats. Epilepsia 2009;50:72-82
80. Porta N, Bourgois B, Galabert C, et al. Anticonvulsant effects of linoleic acid are unrelated to brain phospholipid cell membrane compositions. Epilepsia 2009;50:65-71
81. Diano S, Horvath TL. Anticonvulsant effects of leptin in epilepsy. J Clin Invest 2008;118:26-28
82. Hansen IL, Levy MM, Kerr DS. The 2-deoxyglucose test as a supplement to fasting for detection of childhood hypoglycemia. Pediatr Res 1984;18:359-364
83. Garriga-Canut M, Schoenike B, Qazi R, et al. 2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Nat Neurosci 2006;9:1382-1387
84. Stafstrom CE, Ockuly JC, Murphree L, et al. Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models. Ann Neurol 2009;65:435-447
85. 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 2003;75:675-686
86. Ward J, Caprio V. A radical mediated approach to the core structure of huperzine A. Tetrahedron Lett 2006;47:553-556
87. Coleman BR, Ratcliffe RH, Oguntayo SA, et al. [+]-Huperzine A treatment protects against N-methyl-D-aspartate-induced seizure/status epilepticus in rats. Chem Biol Interact 2008;175:387-395
88. Kimber-Trojnar Z, Borowicz KK, Małek R, et al. Perspectives of losigamone in epilepsy treatment. Pol J Pharmacol 2003;55:675-682
89. Baulac M, Klement S; Losigamone Study Group. Efficacy and safety of Losigamone in partial seizures: a randomized double-blind study. Epilepsy Res 2003;55:177-189
90. Mazarati A, Lundström L, Sollenberg U, et al. 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 2006;318:700-708
91. Mazarati A, Langel U, Bartfai T. Galanin: an endogenous anticonvulsant? Neuroscientist 2001;7:506-517
92. Adkins EM, Smith MD, Pruess T, et al. NAX-5055: a metabolically stable galanin-based neuropeptide with potent anticonvulsant and antinociceptive actions. Epilepsia 2007;48(Suppl 6):, 292 Available from: http://clinicaltrials. gov/ct2/show/NCT00616148 [Last access 26 October 2009]
93. Perucca E, French J, Bialer M. Development of new antiepileptic drugs: challenges, incentives, and recent advances. Lancet Neurol 2007;6:793-804
94. Zaccara G, Franciotta D, Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs. Epilepsia 2007;48:1223-1244
95. Rogawski MA, Löscher W. The neurobiology of antiepileptic drugs. Nat Rev Neurosci 2004;5:553-564
96. Schmidt D, Rogawski MA. New strategies for the identification of drugs to prevent the development or progression of epilepsy. Epilepsy Res 2002;50:71-78 (Pubitemid 34876588)
97. Pitkänen A, Kubova H. Antiepileptic drugs in neuroprotection. Expert Opin Pharmacother 2004;5:777-98
98. Landmark CJ. Targets for antiepileptic drugs in the synapse. Med Sci Monit 2007;13:RA1-7