Epilepsy: the next generation drugs (a review)
Epilepsy is a disease characterized by spontaneous recurrence of unprovoked seizures. Seizures and epilepsy are different disorders, and the terms should not be used interchangeably. It is not accurate to refer to seizures as epilepsy, although “seizure disorder” refers to epilepsy. Seizures are common and are treated in all branches of medicine. Approximately 10% of the population will have one or more seizures during their lifetime. Seizures are symptoms that occur in acute illness, i.e., provoked seizures, or in epilepsy, ie, unprovoked seizures. Antiepileptic drugs (AEDs) are pharmacologic agents used to reduce the frequency of epileptic seizures. “Antiepileptic” drug is a misnomer, because these drugs are effective as symptomatic treatment of seizures, i.e., the symptoms of epilepsy, not as treatment of epilepsy itself. Recent discoveries in molecular biology and genetics have elucidated a genetic basis for some epilepsy syndromes, which will lead to new treatments. This review include new AEDs viz; Ganaxolone, Eslicarbazepine acetate, Fluorofelbamate, Huperzine A, Carisbamate (RWJ-333369), Brivaracetam (ucb 34714), 2-Deoxy-D-glucose, Retigabine, T2000 , T2007, Valrocemide, Tonabersat (SB-220453), YKP3089, Propyl isopropyl acetamide, JZP-4, ICA-105665, NAX-5055, Perampanel and Valpromide.
2. Haerer AF, Anderson DW, Schoenberg BS. Prevalence and clinical features of epilepsy in a biracial United States population. Epilepsia. 1986; 27:66-75.
3. Hauser WA, Annegers JF, Rocca WA. Descriptive epidemiology of epilepsy: contributions of population-based studies from Rochester, Minnesota. Mayo Clin Proc. 1996; 71:578-86.
4. Hauser WA, Annegers JF, Kurland LT. The prevalence of epilepsy in Rochester, Minnesota: 1940-1980. Epilepsia. 1991; 32:429-45.
5. Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935-1984. Epilepsia. 1993; 34:453-68.
6. Annegers JF, Rocca WA, Hauser WA. Causes of epilepsy: contributions of the Rochester epidemiology project. Mayo Clin Proc. 1996; 71:570-575.
7. Nohria V, Giller E, Ganaxolone. Neurotherapeutics. 2004; 4:102-105.
8. Carter R.B, Wood P.L, Wieland S, Hawkinson J.E, Belelli D, Lambert J.J, White H.S, Wolf H.H, Mirsadeghi S, Tahir S.H, Bolger M.B, Lan N.C, Gee K.W, 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. 1997; 280:1284 1295.
9. Le´skiewicz M, Budziszewska B, Jaworska-Feil L, Kubera M, Basta-Kaim Lason W, Inhibitory effect of some neuroactive steroids on cocaine-induced kindling in mice. Polish J. Pharmacol. 2003; 55:1131-1136.
10. Rogawski, M.A., Reddy, D.S., 2004. Neurosteroids: endogenous modulators of seizure susceptibility. In: Rho, J.M., Sankar, R., Cavazos, J. (Eds.), Epilepsy: Scientific Foundations of Clinical Practice. Marcel Dekker, New York, pp. 319—355
11. Biagini G, Baldelli E, Longo D, Pradelli L, Zini I, Rogawski M.A, Avoli M, Endogenous neurosteroids modulate epileptogenesis in a model of temporal lobe epilepsy. Exp. Neurol. 2006; 201:519-524.
12. Benes J, Parada A, Figueiredo A.A, Alves P.C. Freitas A.P, Learmonth D.A, Cunha R.A, Garrett J, Soares-da-Silva P, Anticonvulsant and sodium channel-blocking properties of novel 10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide derivatives. J. Med. Chem. 1999; 42:2582-2587.
13. Ambrosio A.F, Silva A.P, Araujo I, Malva J.O, Soaresda- Silva P, Carvalho A.P, Carvalho C.M, Neurotoxic/ neuroprotective profile of carbamazepine, oxcarbazepine and two new putative antiepileptic drugs, BIA 2-093 and BIA 2-024. Eur. J. Pharmacol. 2000; 406:191–201.
14. Cunha R.A, Coelho J.E, Costenla A.R, Lopes L.V, Parada A, de Mendonca A, Sebastiao A.M, Ribeiro J.A, Effects of carbamazepine and novel 10,11-dihydro-5H dibenz[b,f]azepine- 5-carboxamide derivatives on synaptic transmission in rat hippocampal slices. Pharmacol. Toxicol. 2002; 90:208–213.
15. Almeida L, Soares-da-Silva P, Eslicarbazepine acetate (BIA 2-093). Neurotherapeutics. 2007; 4:88-96.
16. Ward J, Caprio V, A radical mediated approach to the core structure of Huperzine A. Tetrahedron Lett. 2006; 47: 553—556.
17. Bialer M, Johannessen S.I, Kupferberg H.J, Levy R.H, Perucca E, Tomson T, Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII). Epilepsy Res. 2004; 61:1-48.
18. Wallis R.A, Panizzon K.L, Niquet J, Masaratis L, Baldwin R, Wasterlain C.G, Neuroprotective effects of the anticonvulsant, fluorofelbamate. Epilepsia. 2000; 41(7):162.
19. White H.S, Schachter S, Lee D, Xiaoshen J, Eisenberg D, Anticonvulsant activity of Huperzine A, an alkaloid extract of Chinese club moss (Huperzia serrata). Epilepsia. 2005; 46(8):220.
20. Zangara, A, The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuro-protective properties of interest in the treatment of Alzheimer’s disease. Pharmacol. Biochem. Behav. 2003; 75:675-686.
21. 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. 2006; 27.
22. Grabenstatter H.L, Dudek F.E, A new potential AED, carisbamate, substantially reduces spontaneous motor seizures in rats with kainate-induced epilepsy. Epilepsia. 2008; 49:1787-1794.
23. Niespodziany I, Leclere N, Matagne A, Wolff C, Brivaracetam modulates Na+ currents expressed in a neuroblastoma cell line compared with carbamazepine. Epilepsia 2009; 50:107.
24. Kaminski R.M, Matagne A, Leclercq K, Gillard M, Michel P, Kenda B, Talaga P, 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. 2008; 54:715—720.
25. Matagne A, Margineanu D.G, Kenda B, Michel P, Klitgaard H, Anti-convulsive and anti-epileptic properties of brivaracetam (ucb 34714), a high-affinity ligand for the synaptic vesicle protein, SV2A. Br. J. Pharmacol. 2008a; 154:1662-1671.
26. Berwick J, Johnston D, Jones M, Martindale J, Martin C, Kennerly AJ, Redgrave P, 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. 2008; 99:787—798.
27. Rundfeldt C, Netzer R, The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells transfected with human KCNQ2/3 subunits. Neurosci. Lett. 2000; 282:73-76.
28. Spiegelstein O, Yagen B, Bialer M, Structure pharmacokinetic- pharmacodynamic relationships of the new antiepileptic drug valproyl glycinamide. Epilepsia.1999; 40:545–552.
29. Bialer M, Johannessen S.I, Kupferberg H.J, Levy R.H, Loiseau P, Perucca E, Progress report on new antiepileptic drugs: a summary of the Fourth Eilat Conference (EILATV). Epilepsy Res. 2001; 43:11-58.
30. Bialer M, Johannessen S.I, Kupferberg H.J, Levy R.H, Loiseau P, Perucca E, Progress report on new antiepileptic drugs: a summary of the Sixth Eilat Conference (EILAT VI). Epilepsy Res. 2002; 51:31-71.
31. Bialer M, Johannessen S.I, Kupferberg H.J, Levy R.H, Perucca E, Tomson T, Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII). Epilepsy Res. 2004; 61:1-48.
32. Parsons A.A, Bingham S, Raval P, Read S, Thompson M, Upton N, Tonabersat (SB-220453) a novel benzopyran with anticonvulsant properties attenuates trigeminal nerve induced neurovascular reflexes. Br. J. Pharmacol. 2001; 132: 1549-1557.
33. Bialer M, Johannessen S.I, Kupferberg H.J, Levy R.H, Perucca E, Tomson T, Progress report on new antiepileptic drugs: a summary of the tenth Eilat Conference (EILAT X). Epilepsy Res. 2010, 92:89-124.
34. Bialer M, Clinical pharmacology of valpromide. Clin. Pharmacokinet. 1991; 20:114-122.
35. Bialer M, Johannessen S, Kupferberg H.J, Levy R.H, Perucca E, Tomson T, Progress report on new antiepileptic drugs: a summary of the Eighth Eilat Conference (EILAT VIII). Epilepsy Res. 2007; 73:1-52.
36. Funk A.P, Ricci R, Anderson B.A, Arana A.B, De Colle C, Wang S, George M.S, Single doses of JZP-4 decrease cortical excitability. A transcranial magnetic stimulation study. In: American Epilepsy Society 2008 Annual Meeting.
37. Binnie C.D, Kasteleijn-Nolst Trenité D.G.A, De Korte R.A, Photosensitivity as a model for acute antiepileptic drug studies. Electroencephalogr. Clin. Neurophysiol. 1986; 63:35-41.
38. White H.S, Scholl E.A, Klein B.D, Flynn S.P, Pruess T.H, Green B.R, Zhang L, Bulaj, G, 2009. Developing novel antiepileptic drugs: characterization of NAX 5055, a systemically active galanin analog, in epilepsy models. Neurotherapeutics. 2009; 6:372-380.
39. Hashizume Y, Hanada T, Ogasawara A, Ueno M, Nishizawa Y, 2008. Anticonvulsant activity of perampanel, a selective AMPA receptor antagonist, in rodent models of epileptic seizure. In: Poster P02.113 presented at the 60th Annual Meeting of the American Academy of Neurology.
40. Shaltiel, G, Shirley M, Ora K, Belmaker R.H, Agam G, Effect of valproate derivatives on human brain myo-inositol- 1-phosphate (MIP) synthase activity and amphetamine-induced rearing. Pharmacol. Report. 2007; 59:402-407.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeÂ The Effect of Open Access).