Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain: Relationship to anti-convulsant properties

European Journal of Pharmacology

Volumn 664, Issue 1-3, 2011, Pages 36-44

  Gillard, Michel ^a   Fuks, Bruno ^a,b   Leclercq, Karine ^a   Matagne, Alain ^a  

^a UCB PHARMA   (Belgium)

^b GLAXOSMITHKLINE BIOLOGICALS   (Belgium)

Author keywords

Antiepileptic; Brivaracetam; Levetiracetam; SV2A; Synaptic vesicle

Indexed keywords

2 2 [4 (3 AZIDOPHEYL) 2 OXO 1 PYRROLIDINYL]BUTANAMIDE; ANTICONVULSIVE AGENT; BRIVARACETAM; ETIRACETAM; RECOMBINANT PROTEIN; RECOMBINANT SYNAPTIC VESICLE PROTEIN 2A; UCB 100230 1; UCB 30889; UCB 34713; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTICONVULSANT ACTIVITY; ARTICLE; BINDING AFFINITY; BINDING KINETICS; BINDING SITE; CELL LABELING; CONTROLLED STUDY; DOSE TIME EFFECT RELATION; DRUG BINDING; DRUG DOSE TITRATION; DRUG POTENCY; DRUG SELECTIVITY; EX VIVO STUDY; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; LIGAND BINDING; MALE; MOUSE; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; SEIZURE;

ANIMALS; ANTICONVULSANTS; BINDING, COMPETITIVE; BRAIN; CEREBRAL CORTEX; CHO CELLS; CRICETINAE; CRICETULUS; DOSE-RESPONSE RELATIONSHIP, DRUG; EPILEPSY, REFLEX; FEMALE; HUMANS; KINETICS; LIGANDS; MALE; MEMBRANE GLYCOPROTEINS; MICE; NERVE TISSUE PROTEINS; PROTEIN BINDING; PYRROLIDINONES; RATS; SEIZURES; SUBSTRATE SPECIFICITY;

EID: 79957889858     PISSN: 00142999     EISSN: 18790712     Source Type: Journal    
DOI: 10.1016/j.ejphar.2011.04.064     Document Type: Article

References (23)

1. Bajjalieh, S.M., Peterson, K., Shinghal, R., Scheller, R.H., 1992. SV2, a brain synaptic vesicle protein homologous to bacterial transporters. Science 257, 1271-1273.
2. Cheng, Y., Prusoff, W.H., 1973. Relationship between the inhibition constant (k1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22, 3099-3108.
3. French, J.A., Pedley, T.A., 2008. Clinical practice. Initial management of epilepsy. N Engl J Med 359, 166-176. (Pubitemid 351962040)
4. French, J.A., Costantini, C., Brodsky, A., von Rosenstiel, P., 2010. Adjunctive brivaracetam for refractory partial-onset seizures. Neurology 75, 519-525.
5. Gillard, M., Fuks, B., Michel, P., Vertongen, P., Massingham, R., Chatelain, P., 2003. Binding characteristics of [3H]Ucb 30889 to levetiracetam binding sites in rat brain. Eur J Pharmacol 478, 1-9. (Pubitemid 38366068)
6. Gillard, M., Chatelain, P., Fuks, B., 2006. Binding characteristics of levetiracetam to synaptic vesicle protein 2A (SV2A) in human brain and in CHO cells expressing the human recombinant protein. Eur J Pharmacol 536, 102-108.
7. Holyoake, J., Sansom, M.S., 2007. Conformational change in an MFS Protein: MD simulations of LacY. Structure 15, 873-884. (Pubitemid 47042433)
8. Kaminski, R.M., Matagne, A., Leclercq, K., Gillard, M., Michel, P., Kenda, B., Talaga, P., Klitgaard, H., 2008. 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, 715-720.
9. Kaminski, R.M., Matagne, A., Patsalos, P.N., Klitgaard, H., 2009. Benefit of combination therapy in epilepsy: a review of the preclinical evidence with levetiracetam. Epilepsia 50, 387-397.
10. Kasteleijn-Nolst Trenite, D.G., Genton, P., Parain, D., Masnou, P., Steinhoff, B.J., Jacobs, T., Pigeolet, E., Stockis, A., Hirsch, E., 2007. Evaluation of brivaracetam, a novel SV2A ligand, in the photosensitivity model. Neurology 69, 1027-1034. (Pubitemid 47366057)
11. Kenda, B.M., Matagne, A.C., Talaga, P.E., Pasau, P.M., Differding, E., Lallemand, B.I., Frycia, A.M., Moureau, F.G., Klitgaard, H.V., Gillard, M.R., Fuks, B., Michel, P., 2004. Discovery of 4-substituted pyrrolidone butanamides as new agents with significant antiepileptic activity. J Med Chem 47, 530-549. (Pubitemid 38129712)
12. Klitgaard, H., Verdru, P., 2007. Levetiracetam: the first SV2A ligand for the treatment of epilepsy. Expert Opin Drug Discov 2, 1537-1545. (Pubitemid 350192820)
13. Lynch, B.A., Lambeng, N., Nocka, K., Kensel-Hammes, P., Bajjalieh, S.M., Matagne, A., Fuks, B., 2004. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci USA 101, 9861-9866. (Pubitemid 38869327)
14. Lynch, B.A., Matagne, A., Brannstrom, A., von Euler, A., Jansson, M., Hauzenberger, E., Soderhall, J.A., 2008. Visualization of SV2A conformations in situ by the use of protein tomography. Biochem Biophys Res Commun 375, 491-495.
15. Malawska, B., Kulig, K., 2008. Brivaracetam: a new drug in development for epilepsy and neuropathic pain. Expert Opin Investig Drugs 17, 361-369. (Pubitemid 351578188)
16. Matagne, A., Margineanu, D.G., Kenda, B., Michel, P., Klitgaard, H., 2008. Anti-Convulsive and Anti-Epileptic Properties of Brivaracetam (Ucb 34714), a High-Affinity Ligand for the Synaptic Vesicle Protein, SV2A. Br. J. Pharmacol.154, 1662-1671.
17. Meldrum, B.S., Rogawski, M.A., 2007. Molecular targets for antiepileptic drug development. Neurotherapeutics 4, 18-61. (Pubitemid 46107329)
18. Molinoff, P.B., Wolfe, B.B., Weiland, G.A., 1981. Quantitative analysis of drug-receptor interactions: II. determination of the properties of receptor subtypes. Life Sci 29, 427-443. (Pubitemid 11005430)
19. Noyer, M., Gillard, M., Matagne, A., Henichart, J.P., Wulfert, E., 1995. The novel antiepileptic drug levetiracetam (Ucb L059) appears to act via a specific binding site in CNS membranes. Eur J Pharmacol 286, 137-146.
20. Sargentini-Maier, M.L., Rolan, P., Connell, J., Tytgat, D., Jacobs, T., Pigeolet, E., Riethuisen, J.M., Stockis, A., 2007. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after single increasing oral doses in healthy males. Br J Clin Pharmacol 63, 680-688. (Pubitemid 46753569)
21. Sargentini-Maier, M.L., Espie, P., Coquette, A., Stockis, A., 2008. Pharmacokinetics and metabolism of 14C-brivaracetam, a novel SV2A ligand, in healthy subjects. Drug Metab Dispos 36, 36-45.
22. van Paesschen, W., Brodsky, A., 2007. Efficacy and tolerability of 50 and 150 mg/day brivaracetam (Ucb 34714) as adjunctive treatment in adults with refractory partial-onset epilepsy. Epilepsia 48, 329.
23. + currents in rat cortical neurons in culture. Epilepsy Res 88, 46-54.