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

doi:10.1016/j.eplepsyres.2010.09.001

Epilepsy Research

Volume 92, Issues 2–3, December 2010, Pages 89-124

https://doi.org/10.1016/j.eplepsyres.2010.09.001 Get rights and content

Summary

The Tenth Eilat Conference on New Antiepileptic Drugs (AEDs)-EILAT X, took place in Eilat, Israel from the 25th to 29th of April 2010. About 200 basic scientists, clinical pharmacologists and neurologists from 25 countries attended the conference, whose main themes included learning from the past: Lessons learnt after 18 years of Eilat Conferences and Detecting assessing and preventing adverse effects of AEDs. Consistent with previous formats of this conference, a large part of the program was devoted to a review of AEDs in development, as well as updates on AEDs introduced since 1994. Like the previous EILAT (EILAT IX) manuscript, the current (EILAT X) manuscript focuses only on the preclinical and clinical pharmacology of AEDs that are currently in development. These include brivaracetam, carisbamate, 2-deoxy-glucose, ganaxolone, huperizine A, ICA-105665, NAX-5055, retigabine, perampanel, T-2007, valnoctamide and YK3089. Since the previous Eilat Conference (EILAT IX-2008) two new AEDs; eslicarbazepine acetate and lacosamide have been marketed and three new AEDs in development not included in the EILAT IX manuscript were added: ICA-105665, perampanel and valnoctamide. The CNS efficacy of these compounds in anticonvulsant animal models as well as other disease model systems are presented in Table 1, Table 2 and their proposed mechanism of action at summarized in Table 3.

Section snippets

Brivaracetam (ucb34714)

S. Lu^a, A. Stockis^b, A. Matagne^b, M. Johnson^a

^aUCB Inc., Raleigh, NC, USA

^bUCB Pharma SA, Braine-l’Alleud, Belgium

Carisbamate (RWJ-333369)

G.P. Novak^a, M. Kao^a, H.S. White^b, B.D. Klein^c, P. Zannikos^a

^aJohnson & Johnson, Pharmaceutical Research & Development L.L.C., Titusville, New Jersey, USA

^bDepartment of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT

^cNeuroAdjuvants, Inc. Salt Lake City, UT, USA

2-Deoxy-d-glucose

T.P. Sutula

Department of Neurology, University of Wisconsin, Madison, WI, and NeuroGenomex, Inc., Madison, WI, USA

Ganaxolone

V. Nohria^d, J. Tsai^a, K. Shaw^a, M.A. Rogawski^b, V.A. Pieribone^a,c, G. Farfel^a

^aMarinus Pharmaceuticals, Inc., Branford, CT, USA

^bDepartment of Neurology, School of Medicine, University of California, Davis, Sacramento, CA, USA

^cThe John B. Pierce Laboratory and Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, USA

^dMercer University, Atlanta, GA, USA

Huperzine A

S.C. Schachter^a, D. Ekstein^a,b, P. Park^c, T. Yaksh^c, H. S. White^d, J. Stables^e

^aHarvard Medical School, Boston, MA, USA

^bHadassah University Medical Center, Jerusalem, Israel

^cUCSD, San Diego, CA, USA

^dUniversity of Utah, Salt Lake City, UT, USA

^eAnticonvulsant Screening Project, NINDS, NIH, Bethesda, MD, USA

ICA-105665

C.R. Rigdon, S.V. Hetherington, E.L. Moore R. Roeloffs, W.M. Harrison, A.C. Gerlach

Icagen, Inc., Durham, NC, USA

NAX-5055

B. Klein^c, G. Bulaj^a,c, E. Grussendorf^b, M. Smith^b, J. Grussendorf^b, E. Adkins-Scholl^c, H.S. White^b,c

^aDepartment of Medicinal Chemistry, University of Utah, Salt Lake City, UT

^bDepartment of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT

^cNeuroAdjuvants, Inc., Salt Lake City, UT, USA

Perampanel (E2007)

Jina Swartz, Antonio Laurenza

Eisai Medical Research, Ridgefield Park, NJ, USA

Retigabine

J.M.J. Hammond

Valeant Pharmaceuticals International

T2007 (sodium 5,5-diphenylbarbiturate)

A. Yacobi^a, J. French^b, D. Moros^a, H. Rutman^a, D. Ganes^a, G. McKay^d, A. Raines^c, B. Levitt^a

^aTaro Pharmaceuticals U.S.A., Inc., 3 Skyline Drive, Hawthorne, NY 10532, USA

^bNew York University Comprehensive Epilepsy Center, The Epilepsy Study Consortium, 223 East 34th Street, New York, NY 10016, USA

^cPharmacology, Georgetown University, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20057, USA

^dPharmalytics Ltd., 346-111 Research Drive, Saskatoon, SK S7N 3R2, Canada

Valproic acid 2nd generation derivatives

M. Bialer, B. Yagen

Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jeruslaem, Israel

YKP3089

S. James Lee, Susan Melnick, Zhaoping Yan, Lin-Ming Shen, Martin Brecher

SK Life Science Inc., Fair Lawn, New Jersey, USA

Acknowledgement

SK Life Science Inc. gratefully acknowledges the support of the Anticonvulsant Screening Program at NIH/NINDS.

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ReviewProgress report on new antiepileptic drugs: A summary of the Tenth Eilat Conference (EILAT X)

Summary

Section snippets

Brivaracetam (ucb34714)

Carisbamate (RWJ-333369)

2-Deoxy-d-glucose

Ganaxolone

Huperzine A

ICA-105665

NAX-5055

Perampanel (E2007)

Retigabine

T2007 (sodium 5,5-diphenylbarbiturate)

Valproic acid 2nd generation derivatives

YKP3089

Acknowledgement

Epilepsy Res.

Exp. Neurol.

Neurotherapeutics

Epilepsy Res.

Electroencephalogr. Clin. Neurophysiol.

Behav. Brain Res.

Epilepsy Res.

Pharmacol. Ther.

Eur. J. Pharmacol.

Neuropharmacology

Neuropharmacology

Epilepsy Res.

Epilepsy Res.

Epilepsy Res.

Epilepsy Res.

Brain Res.

Neuroscience

Neuropeptides

Neurotherapeutics

Tox. Appl. Pharm.

Int. J. Rad. Onc. Biol. Phys.

Neurotherapeutics

Neurosci. Lett.

Tetrahedron: Asymm.

Epilepsy Res.

Neurosci. Lett.

Pathogenesis and pharmacology of epilepsy in the lithium-pilocarpine model

Epilepsia

Stereoselective pharmacokinetic analysis of valnoctamide in healthy subjects and epileptic patients

Clin. Pharmacol. Ther.

Valnoctamide as valproate substitute with low teratogenic potential in mania: a double-blind, controlled, add-on clinical trial

Bipolar Disorder

Fine detail of neurovascular coupling revealed by spatio-temporal analysis of the hemodynamic response to single whisker stimulation in rat barrel cortex

J. Neurophysiol.

Neurosteroids and epilepsy

Curr. Opin. Neurol.

Neurosteroids and epileptogenesis in the pilocarpine model: evidence for a relationship between P450scc induction and length of the latent period

Epilepsia

Key factors in the discovery and development of new antiepileptic drugs (AEDs)

Nature Rev. Drug Discov.

Brivaracetam as adjunctive treatment of refractory partial-onset seizures in adults: results from two randomized, double-blind, placebo-controlled trials

Epilepsia

Retigabine 600 or 900 mg/day as adjunctive therapy in adults with refractory partial-onset seizures

Eur. J. Neurol.

Safety and tolerability of brivaracetam (ucb 34714) as adjunctive treatment in adults with refractory partial-onset seizures

Epilepsia

Design, synthesis, and characterization of high-affinity, systemically-active galanin analogues with potent anticonvulsant activities J

Med. Chem.

Characterization of the anticonvulsant properties of ganaxolone (CCD 1042; 3(-hydroxy-3(-methyl-5(-pregnan-20-one), a selective, high-affinity, steroid modulator of the gamma-aminobutyric acidA receptor

J. Pharmacol. Exp. Ther.

Pharmacokinetic interaction study between the new antiepileptic and CNS drug RWJ-333369 and carbamazepine in healthy adults

Epilepsia

An interaction study between the new antiepileptic and CNS drug carisbamate (RWJ-333369) and lamotrigine and valproic acid

Epilepsia

AMPA receptor antagonists as potential anticonvulsant drugs

Curr. Top. Med. Chem.

Randomized, controlled, dose-ranging trial of carisbamate for partial-onset seizures

Neurology

A new drug, RWJ-333369, protects limbic areas in the lithium-pilocarpine model (lipilo) of epilepsy and delays or prevents the occurrence of spontaneous seizures (abstract)

Epilepsia

Effects of carisbamate (RWJ-333369) in two models of genetically determined generalized epilepsy, the GAERS and the audiogenic Wistar AS

Epilepsia

Retigabine 1200 mg/day as adjunctive therapy in adults with refractory partial-onset seizures

Eur. J. Neurol.

Review
Progress report on new antiepileptic drugs: A summary of the Tenth Eilat Conference (EILAT X)