α-Substituted Lactams and Acetamides: Ion Channel Modulators that Show Promise in Treating Drug-resistant Epilepsy

Author(s): Arcadius V. Krivoshein*

Journal Name: Central Nervous System Agents in Medicinal Chemistry
Formerly Current Medicinal Chemistry - Central Nervous System Agents

Volume 20 , Issue 2 , 2020


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Graphical Abstract:


Abstract:

The two main problems in the pharmacotherapy of epilepsy are resistance to currently available first-line medications (which occurs in about one third of patients) and the high incidence of side effects. To address these two challenges, extensive efforts are being undertaken to design new, structurally distinct antiepileptic drugs with a broad spectrum of anticonvulsant activity. Tests in animal models of epilepsy indicate that α-substituted lactams and acetamides show a broad spectrum of anticonvulsant activity (including very promising activity in drug-resistant models) as well as an excellent safety profile. Limited clinical results confirm these preclinical findings. In the first part of this review, pharmacology and toxicology of α-substituted lactams and acetamides and their putative protein targets in the brain have been discussed. This is followed by a discussion of structure-activity relationships among α-alkyl-, α-aryl-, and α-aryl-α-alkyl-substituted derivatives. The most promising structures seem to be those related to 3-ethyl-3-phenylpyrrolidin-2-one, 2-phenylbutyramide, and 2- sec-butylvaleramide. The information presented in this review is expected to facilitate rational drug design and development efforts for α-substituted lactams and acetamides.

Keywords: Lactams, acetamides, antiepileptic drugs, medically refractory epilepsy, pharmacophore, neurotransmitter receptors, ion channels.

[1]
Macdonald, R.L.; McLean, M.J. Anticonvulsant drugs: Mechanisms of action. Adv. Neurol., 1986, 44, 713-736.
[PMID: 2871724]
[2]
Avanzini, G.; Regesta, G.; Tanganelli, P.; Avoli, M. Molecular and Cellular Targets for Anti-Epileptic Drugs; John Libbey & Co.: London, 1997.
[3]
Meldrum, B.S.; Rogawski, M.A. Molecular targets for antiepileptic drug development. Neurotherapeutics, 2007, 4(1), 18-61.
[http://dx.doi.org/10.1016/j.nurt.2006.11.010] [PMID: 17199015]
[4]
Mula, M. New antiepileptic drugs: Molecular targets. Cent. Nerv. Syst. Agents Med. Chem., 2009, 9(2), 79-86.
[http://dx.doi.org/10.2174/187152409788452063] [PMID: 20021341]
[5]
White, H.S.; Rho, J.M. Mechanism of Action of Antiepileptic Drugs. Professional Communications Inc; West Islip, 2010.
[6]
Ghasemi, M.; Schachter, S.C. The NMDA receptor complex as a therapeutic target in epilepsy: A review. Epilepsy Behav., 2011, 22(4), 617-640.
[http://dx.doi.org/10.1016/j.yebeh.2011.07.024] [PMID: 22056342]
[7]
Rogawski, M.A. AMPA receptors as a molecular target in epilepsy therapy. Acta Neurol. Scand. Suppl., 2013, 127(s197), 9-18.
[http://dx.doi.org/10.1111/ane.12099] [PMID: 23480151]
[8]
Löscher, W.; Gillard, M.; Sands, Z.A.; Kaminski, R.M.; Klitgaard, H. Synaptic vesicle glycoprotein 2A ligands in the treatment of epilepsy and beyond. CNS Drugs, 2016, 30(11), 1055-1077.
[http://dx.doi.org/10.1007/s40263-016-0384-x] [PMID: 27752944]
[9]
Ghasemi, M.; Hadipour-Niktarash, A. Pathologic role of neuronal nicotinic acetylcholine receptors in epileptic disorders: Implication for pharmacological interventions. Rev. Neurosci., 2015, 26(2), 199-223.
[http://dx.doi.org/10.1515/revneuro-2014-0044] [PMID: 25565544]
[10]
Close, W.J.; Spielman, M.A. Anticonvulsant drugs. In: Medicinal Chemistry; Hartung, W.H., Ed.; John Wiley & Sons: New York, 1961; Vol. 5, pp. 1-349.
[11]
Vida, J.A. Anticonvulsants; Academic Press: New York, 1977.
[12]
Krivoshein, A.V. Anticonvulsants based on the α-substituted amide group pharmacophore bind to and inhibit function of neuronal nicotinic acetylcholine receptors. ACS Chem. Neurosci., 2016, 7(3), 316-326.
[http://dx.doi.org/10.1021/acschemneuro.5b00259] [PMID: 26741746]
[13]
Ngugi, A.K.; Bottomley, C.; Kleinschmidt, I.; Sander, J.W.; Newton, C.R. Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. Epilepsia, 2010, 51(5), 883-890.
[http://dx.doi.org/10.1111/j.1528-1167.2009.02481.x] [PMID: 20067507]
[14]
Epilepsy: A Public Health Imperative; World Health Organization: Geneva, 2019. https://www.who.int/mental_health/neurology/epilepsy/report_20199/en/
[15]
Zack, M.M.; Kobau, R. National and state estimates of the numbers of adults and children with active epilepsy - United States, 2015. MMWR Morb. Mortal. Wkly. Rep., 2017, 66(31), 821-825.
[http://dx.doi.org/10.15585/mmwr.mm6631a1] [PMID: 28796763]
[16]
Brodie, M.J.; Barry, S.J.E.; Bamagous, G.A.; Norrie, J.D.; Kwan, P. Patterns of treatment response in newly diagnosed epilepsy. Neurology, 2012, 78(20), 1548-1554.
[http://dx.doi.org/10.1212/WNL.0b013e3182563b19] [PMID: 22573629]
[17]
Frey, H.-H.; Janz, D. Antiepileptic Drugs. Springer-Verlag: Berlin, 1985, pp. 867.
[18]
Levy, R.H.; Mattson, R.H.; Meldrum, B.S. Antiepileptic Drugs; Raven Press: New York, 1995.
[19]
Spielman, M.A. Some anticonvulsants. Proceedings of the 1st National Medicinal Chemistry Symposium of the American Chemical Society, Ann Arbor, MIJune 17-19, 1948, pp. 119-124.
[20]
Kaufman, I.C. Types of epilepsy and their treatment. Dis. Nerv. Syst., 1950, 11(4), 99-106.
[21]
Jenney, E.H.; Lee, L.D.; Williams, H.L.; Pfeiffer, C.C. Pharmacology and anticonvulsant spectrum of atrolactamide (M-144) (Themisone). J. Pharmacol. Exp. Ther., 1952, 106, 398.
[22]
Marshall, W.H.; Jenney, E.H.; Pfeiffer, C.C. Pharmacology and anticonvulsant spectrum of acrolactamide (Themisone). AMA Arch. Neurol. Psychiatry, 1953, 69(6), 770-771.
[PMID: 13050230]
[23]
Stamps, F.W.; Marshall, W.H.; Orloff, M.J.; Gibbs, F.A.; Pfeiffer, C.C. Treatment of three hundred epileptic patients with acrolactamide. AMA Arch. Neurol. Psychiatry, 1953, 69(6), 771-772.
[PMID: 13050233]
[24]
Marshall, F.J. Some 3,3-disubstituted-2-pyrrolidinones. J. Org. Chem., 1958, 23(3), 503-505.
[http://dx.doi.org/10.1021/jo01097a619]
[25]
Gruber, C.M., Jr; Mosier, J.M.; Gibson, W.R. Drugs and epilepsy--motor seizures. Arch. Int. Pharmacodyn. Ther., 1959, 121(3-4), 443-458.
[PMID: 13829770]
[26]
Maffii, G. Attivita’ farmacologica di derivati β-lattamici. Nota I – Azione sedativa, ipnotica ed anticonvulsivante. Farmaco, Sci., 1959, 14(3), 176-193.
[27]
Carraz, G.; Darbon, M.; Lebreton, S.; Bériel, H. Propriétés pharmacodynamiques de l’acide n-dipropyl acétique et de ses dérivés. Quatrième mémoire: Le n-dipropyl acétamide. Therapie, 1964, 19, 468-476.
[PMID: 14138084]
[28]
Lloyd, K.G.; Worms, P. The broad anticonvulsant spectrum of GABAmimetic drugs: Relevance to antiepileptic drug research. Br. J. Pharmacol., 1981, 73, 232-233.
[29]
Brouillette, W.J.; Grunewald, G.L. Synthesis and anticonvulsant activity of some substituted lactams and amides. J. Med. Chem., 1984, 27(2), 202-206.
[http://dx.doi.org/10.1021/jm00368a017] [PMID: 6694169]
[30]
Löscher, W.; Nau, H. Pharmacological evaluation of various metabolites and analogues of valproic acid. Anticonvulsant and toxic potencies in mice. Neuropharmacology, 1985, 24(5), 427-435.
[http://dx.doi.org/10.1016/0028-3908(85)90028-0] [PMID: 3927183]
[31]
Haj-Yehia, A.; Bialer, M. Structure-pharmacokinetic relationships in a series of valpromide derivatives with antiepileptic activity. Pharm. Res., 1989, 6(8), 683-689.
[http://dx.doi.org/10.1023/A:1015934321764] [PMID: 2510141]
[32]
Haj-Yehia, A.; Bialer, M. Structure-pharmacokinetic relationships in a series of short fatty acid amides that possess anticonvulsant activity. J. Pharm. Sci., 1990, 79(8), 719-724.
[http://dx.doi.org/10.1002/jps.2600790814] [PMID: 2231336]
[33]
Meza-Toledo, S.E.; Zenteno-García, M.T.; Juárez-Carvajal, E.; Martínez-Muñoz, D.; Carvajal-Sandoval, G. A new homologous series of anticonvulsants: phenyl alcohol amides. Synthesis and pharmacological evaluation. Arzneimittelforschung, 1990, 40(12), 1289-1291.
[PMID: 2095124]
[34]
Hadad, S.; Bialer, M. Pharmacokinetic analysis and antiepileptic activity of N-valproyl derivatives of GABA and glycine. Pharm. Res., 1995, 12(6), 905-910.
[http://dx.doi.org/10.1023/A:1016277507865] [PMID: 7667199]
[35]
Reddy, P.A.; Hsiang, B.C.H.; Latifi, T.N.; Hill, M.W.; Woodward, K.E.; Rothman, S.M.; Ferrendelli, J.A.; Covey, D.F. 3,3-Dialkyl- and 3-alkyl-3-benzyl-substituted 2-pyrrolidinones: a new class of anticonvulsant agents. J. Med. Chem., 1996, 39(9), 1898-1906.
[http://dx.doi.org/10.1021/jm9600196] [PMID: 8627613]
[36]
Reddy, P.A.; Woodward, K.E.; McIlheran, S.M.; Hsiang, B.C.H.; Latifi, T.N.; Hill, M.W.; Rothman, S.M.; Ferrendelli, J.A.; Covey, D.F. Synthesis and anticonvulsant activities of 3,3-dialkyl- and 3-alkyl-3-benzyl-2-piperidinones (δ-valerolactams) and hexahydro-2H-azepin-2-ones (ε-caprolactams). J. Med. Chem., 1997, 40(1), 44-49.
[http://dx.doi.org/10.1021/jm960561u] [PMID: 9016327]
[37]
Levi, M.; Yagen, B.; Bialer, M. Pharmacokinetics and antiepileptic activity of valproyl hydroxamic acid derivatives. Pharm. Res., 1997, 14(2), 213-217.
[http://dx.doi.org/10.1023/A:1012009012850] [PMID: 9090712]
[38]
Carvajal-Sandoval, G.; Juárez-Carvajal, E.; Cruz-Peinado, C.; Meza-Toledo, S.E. Synthesis and pharmacological evaluation of a new homologous series of (+/-)-p-fluoro-phenyl alcohol amide anticonvulsants. Arzneimittelforschung, 1998, 48(4), 349-352.
[PMID: 9608875]
[39]
Meza-Toledo, S.E.; Juárez-Carvajal, E.; Carvajal-Sandoval, G. Synthesis of a new homologous series of p-chlorophenyl alcohol amides, their anticonvulsant activity and their testing as potential GABAB receptor antagonists. Arzneimittelforschung, 1998, 48(8), 797-801.
[PMID: 9748705]
[40]
White, H.S.; Armstrong, H.; Barton, M.; Artman, L.D. Anticonvulsant profile of NPS 1776: A broad-spectrum anticonvulsant. Epilepsia, 1999, 40(Suppl. 7), 28.
[41]
Spiegelstein, O.; Yagen, B.; Levy, R.H.; Finnell, R.H.; Bennett, G.D.; Roeder, M.; Schurig, V.; Bialer, M. Stereoselective pharmacokinetics and pharmacodynamics of propylisopropyl acetamide, a CNS-active chiral amide analog of valproic acid. Pharm. Res., 1999, 16(10), 1582-1588.
[http://dx.doi.org/10.1023/A:1018960722284] [PMID: 10554101]
[42]
Grimm, J.B.; Stables, J.P.; Brown, M.L. Design, synthesis, and development of novel caprolactam anticonvulsants. Bioorg. Med. Chem., 2003, 11(18), 4133-4141.
[http://dx.doi.org/10.1016/S0968-0896(03)00400-0] [PMID: 12927875]
[43]
Isoherranen, N.; Yagen, B.; Woodhead, J.H.; Spiegelstein, O.; Blotnik, S.; Wilcox, K.S.; Finnell, R.H.; Bennett, G.D.; White, H.S.; Bialer, M. Characterization of the anticonvulsant profile and enantioselective pharmacokinetics of the chiral valproylamide propylisopropyl acetamide in rodents. Br. J. Pharmacol., 2003, 138(4), 602-613.
[http://dx.doi.org/10.1038/sj.bjp.0705076] [PMID: 12598414]
[44]
Choudhury-Mukherjee, I.; Schenck, H.A.; Cechova, S.; Pajewski, T.N.; Kapur, J.; Ellena, J.; Cafiso, D.S.; Brown, M.L. Design, synthesis, and evaluation of analogues of 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide as orally available general anesthetics. J. Med. Chem., 2003, 46(12), 2494-2501.
[http://dx.doi.org/10.1021/jm020546r] [PMID: 12773053]
[45]
Schenck, H.A.; Lenkowski, P.W.; Choudhury-Mukherjee, I.; Ko, S-H.; Stables, J.P.; Patel, M.K.; Brown, M.L. Design, synthesis and evaluation of novel hydroxyamides as orally available anticonvulsants. Bioorg. Med. Chem., 2004, 12(5), 979-993.
[http://dx.doi.org/10.1016/j.bmc.2003.12.011] [PMID: 14980611]
[46]
Meza-Toledo, S.E.; Olea-Gómez, A.; Mora-Ramírez, E.Y.; Peralta-Cruz, J.; Noguerón-Chirinos, J.B. Synthesis and pharmacological evaluation of some DL-dichlorophenyl alcohol amides anticonvulsants. Arzneimittelforschung, 2004, 54(12), 830-834.
[PMID: 15646366]
[47]
Tasso, S.M.; Moon, S.Ch.; Bruno-Blanch, L.E.; Estiú, G.L. Characterization of the anticonvulsant profile of valpromide derivatives. Bioorg. Med. Chem., 2004, 12(14), 3857-3869.
[http://dx.doi.org/10.1016/j.bmc.2004.05.003] [PMID: 15210153]
[48]
Winkler, I.; Sobol, E.; Yagen, B.; Steinman, A.; Devor, M.; Bialer, M. Efficacy of antiepileptic tetramethylcyclopropyl analogues of valproic acid amides in a rat model of neuropathic pain. Neuropharmacology, 2005, 49(8), 1110-1120.
[http://dx.doi.org/10.1016/j.neuropharm.2005.06.008] [PMID: 16055160]
[49]
Bialer, M.; Yagen, B. Valproic acid: second generation. Neurotherapeutics, 2007, 4(1), 130-137.
[http://dx.doi.org/10.1016/j.nurt.2006.11.007] [PMID: 17199028]
[50]
Meza-Toledo, S.E.; Yasutake-Kimoto, L.; Alcalá-Rentería, M.; Domínguez-Rodríguez, M.A.; Jaime-Rodríguez, R.; Nava-Arzaluz, M.G.; Gutiérrez-Laflor, G.; Peralta-Cruz, J.; Carvajal-Sandoval, G. Synthesis of DL-hydroxybenzenamides as anticonvulsants. Arzneimittelforschung, 2008, 58(3), 105-110.
[PMID: 18488805]
[51]
Meza-Toledo, S.E.; Lira-Zárate, F.; Robles-Martínez, E.L.; Peralta-Alvarez, B.; Cabrera-Cedillo, F.; Peralta-Cruz, J.; Cruz-Peinado, C.; Miñón-López, H. Synthesis of DL-fluorobenzenamides as anticonvulsants. Arzneimittelforschung, 2008, 58(4), 155-159.
[PMID: 18540476]
[52]
Kaufmann, D.; Bialer, M.; Shimshoni, J.A.; Devor, M.; Yagen, B. Synthesis and evaluation of antiallodynic and anticonvulsant activity of novel amide and urea derivatives of valproic acid analogues. J. Med. Chem., 2009, 52(22), 7236-7248.
[http://dx.doi.org/10.1021/jm901229s] [PMID: 19877649]
[53]
Pessah, N.; Bialer, M.; Wlodarczyk, B.; Finnell, R.H.; Yagen, B. α-fluoro-2,2,3,3-tetramethylcyclopropanecarboxamide, a novel potent anticonvulsant derivative of a cyclic analogue of valproic acid. J. Med. Chem., 2009, 52(8), 2233-2242.
[http://dx.doi.org/10.1021/jm900017f] [PMID: 19296679]
[54]
White, H.S.; Alex, A.B.; Pollock, A.; Hen, N.; Shekh-Ahmad, T.; Wilcox, K.S.; McDonough, J.H.; Stables, J.P.; Kaufmann, D.; Yagen, B.; Bialer, M. A new derivative of valproic acid amide possesses a broad-spectrum antiseizure profile and unique activity against status epilepticus and organophosphate neuronal damage. Epilepsia, 2012, 53(1), 134-146.
[http://dx.doi.org/10.1111/j.1528-1167.2011.03338.x] [PMID: 22150444]
[55]
Pastore, V.; Sabatier, L.; Enrique, A.; Marder, M.; Bruno-Blanch, L.E. Synthesis and anticonvulsant activity of bioisosteres of trimethadione, N-derivative-1,2,3-oxathiazolidine-4-one-2,2-dioxides from α-hydroxyamides. Bioorg. Med. Chem., 2013, 21(4), 841-846.
[http://dx.doi.org/10.1016/j.bmc.2012.12.033] [PMID: 23321016]
[56]
Pastore, V.; Wasowski, C.; Martin, P.; Enrique, A.; Higgs, J.; Bruno-Blanch, L.E.; Milesi, V.; Marder, M. N-propyl-2,2-diphenyl-2-hydroxyacetamide, a novel α-hydroxyamide with anticonvulsant, anxiolytic and antidepressant-like effects that inhibits voltage-gated sodium channels. Eur. J. Pharmacol., 2018, 819, 270-280.
[http://dx.doi.org/10.1016/j.ejphar.2017.11.048] [PMID: 29217174]
[57]
Krivoshein, A.V.; Guevara, J.L.; Meriano, M.F. Binding of noncompetitive inhibitors to the extracellular domain of neuronal nAChRs: Molecular docking with anticonvulsant α-substituted acetamides and lactams. Proceedings of the Neuroscience 2018 Meeting (48th Annual Meeting of the Society for Neuroscience), San Diego, CA, November 3-7, 2018.
[58]
Tanaka, T.; Yajima, N.; Kiyoshi, T.; Miura, Y.; Inoue, Y.; Nishimaki, T.; Iwama, S. Identification of 2-(2′-fluoro-[1,1′-biphenyl]-2-yl)acetamide as a Sodium Valproate-like broad spectrum anti-epileptic drug candidate. Bioorg. Med. Chem. Lett., 2019, 29(2), 138-142.
[http://dx.doi.org/10.1016/j.bmcl.2018.12.014] [PMID: 30551904]
[59]
Stepansky, W. A clinical study in the use of valmethamide, an anxiety-reducing drug. Curr. Ther. Res. Clin. Exp., 1960, 2(5), 144-147.
[PMID: 13834349]
[60]
Levinger, E. Novonal als Hypnotikum und Sedativum. Dtsch. Med. Wochenschr., 1928, 54(7), 271.
[http://dx.doi.org/10.1055/s-0028-1125040]
[61]
Volwiler, E.H.; Tabern, D.L. Some alkyl and aryl amides and ureides as hypnotics. J. Am. Chem. Soc., 1936, 58(8), 1352-1354.
[http://dx.doi.org/10.1021/ja01299a012]
[62]
Nelson, J.W.; Lyster, S.C.; Cartland, G.F. A pharmacological study of some new synthetic hypnotics. J. Am. Pharm. Assoc. (Sci. Ed), 1941, 30(7), 180-182.
[http://dx.doi.org/10.1002/jps.3030300702]
[63]
Chapman, M.V.A.; Marshall, P.G.; McCrea, P.A.; Sheahan, M.M. Derivatives of acetamide and benzamide as hypnotics. J. Pharm. Pharmacol., 1957, 9(1), 20-28.
[http://dx.doi.org/10.1111/j.2042-7158.1957.tb12250.x] [PMID: 13398903]
[64]
Ko, S-H.; Jochnowitz, N.; Lenkowski, P.W.; Batts, T.W.; Davis, G.C.; Martin, W.J.; Brown, M.L.; Patel, M.K. Reversal of neuropathic pain by α-hydroxyphenylamide: A novel sodium channel antagonist. Neuropharmacology, 2006, 50(7), 865-873.
[http://dx.doi.org/10.1016/j.neuropharm.2005.12.008] [PMID: 16464480]
[65]
Kaufmann, D.; Bates, E.A.; Yagen, B.; Bialer, M.; Saunders, G.H.; Wilcox, K.; White, H.S.; Brennan, K.C. sec-Butylpropylacetamide (SPD) has antimigraine properties. Cephalalgia, 2016, 36(10), 924-935.
[http://dx.doi.org/10.1177/0333102415612773] [PMID: 26568161]
[66]
Grande, F.; Anderson, J.T.; Keys, A. Phenyl butyramide and the serum cholesterol concentration in man. Metabolism, 1957, 6(2), 154-160.
[PMID: 13418341]
[67]
Rossi, B.; Rulli, V. The hypocholesterolemic effect of phenylethylacetic acid amide in hypercholesterolemic atherosclerotic patients. Am. Heart J., 1957, 53(2), 277-283.
[http://dx.doi.org/10.1016/0002-8703(57)90215-6] [PMID: 13394527]
[68]
Wildi, E. Innocuité du traitement prolongé au phényléthylacétamide (PEA). Ther. Umsch., 1961, 18, 211-215.
[PMID: 13785260]
[69]
Krall, R.L.; Penry, J.K.; White, B.G.; Kupferberg, H.J.; Swinyard, E.A. Antiepileptic drug development: II. Anticonvulsant drug screening. Epilepsia, 1978, 19(4), 409-428.
[http://dx.doi.org/10.1111/j.1528-1157.1978.tb04507.x] [PMID: 699894]
[70]
Kehne, J.H.; Klein, B.D.; Raeissi, S.; Sharma, S. The National Institute of Neurological Disorders and Stroke (NINDS) Epilepsy Therapy Screening Program (ETSP). Neurochem. Res., 2017, 42(7), 1894-1903.
[http://dx.doi.org/10.1007/s11064-017-2275-z] [PMID: 28462454]
[71]
Löscher, W. Animal models of seizures and epilepsy: Past, present, and future role for the discovery of antiseizure drugs. Neurochem. Res., 2017, 42(7), 1873-1888.
[http://dx.doi.org/10.1007/s11064-017-2222-z] [PMID: 28290134]
[72]
Barker-Haliski, M.; White, H.S. Validated animal models for antiseizure drug (ASD) discovery: Advantages and potential pitfalls in ASD screening. Neuropharmacology, 2020, 167 article 107750
[http://dx.doi.org/10.1016/j.neuropharm.2019.107750 ] [PMID: 31469995]
[73]
Putnam, T.J.; Merritt, H.H. Experimental determination of the anticonvulsant properties of some phenyl derivatives. Science, 1937, 85(2213), 525-526.
[http://dx.doi.org/10.1126/science.85.2213.525] [PMID: 17750072]
[74]
Toman, J.E.; Swinyard, E.A.; Goodman, L.S. Properties of maximal seizures, and their alteration by anticonvulant drugs and other agents. J. Neurophysiol., 1946, 9, 231-239.
[http://dx.doi.org/10.1152/jn.1946.9.3.231] [PMID: 21028165]
[75]
Wilcox, K.S.; Dixon-Salazar, T.; Sills, G.J.; Ben-Menachem, E.; White, H.S.; Porter, R.J.; Dichter, M.A.; Moshé, S.L.; Noebels, J.L.; Privitera, M.D.; Rogawski, M.A. Issues related to development of new antiseizure treatments. Epilepsia, 2013, 54(Suppl. 4), 24-34.
[http://dx.doi.org/10.1111/epi.12296] [PMID: 23909851]
[76]
Barker-Haliski, M.L.; Johnson, K.; Billingsley, P.; Huff, J.; Handy, L.J.; Khaleel, R.; Lu, Z.; Mau, M.J.; Pruess, T.H.; Rueda, C.; Saunders, G.; Underwood, T.K.; Vanegas, F.; Smith, M.D.; West, P.J.; Wilcox, K.S. Validation of a preclinical drug screening platform for pharmacoresistant epilepsy. Neurochem. Res., 2017, 42(7), 1904-1918.
[http://dx.doi.org/10.1007/s11064-017-2227-7] [PMID: 28303498]
[77]
Campos, G.; Fortuna, A.; Falcão, A.; Alves, G. In vitro and in vivo experimental models employed in the discovery and development of antiepileptic drugs for pharmacoresistant epilepsy. Epilepsy Res., 2018, 146, 63-86.
[http://dx.doi.org/10.1016/j.eplepsyres.2018.07.008] [PMID: 30086482]
[78]
Wilcox, K.S.; West, P.J.; Metcalf, C.S. The current approach of the Epilepsy Therapy Screening Program contract site for identifying improved therapies for the treatment of pharmacoresistant seizures in epilepsy. Neuropharmacology, 2020, 166 article 107811
[http://dx.doi.org/10.1016/j.neuropharm.2019.107811] [PMID: 31790717]
[79]
Skerritt, J.H.; Johnston, G.A.; Chow, S.C.; MacDonald, R.L.; Prager, R.H.; Ward, A.D. Differential modulation of γ-aminobutyric acid receptors by caprolactam derivatives with central nervous system depressant or convulsant activity. Brain Res., 1985, 331(2), 225-233.
[http://dx.doi.org/10.1016/0006-8993(85)91548-3] [PMID: 2985202]
[80]
Hill, M.W.; Reddy, P.A.; Covey, D.F.; Rothman, S.M. Contribution of subsaturating GABA concentrations to IPSCs in cultured hippocampal neurons. J. Neurosci., 1998, 18(14), 5103-5111.
[http://dx.doi.org/10.1523/JNEUROSCI.18-14-05103.1998] [PMID: 9651194]
[81]
Catterall, W.A. Sodium channels, inherited epilepsy, and antiepileptic drugs. Annu. Rev. Pharmacol. Toxicol., 2014, 54, 317-338.
[http://dx.doi.org/10.1146/annurev-pharmtox-011112-140232] [PMID: 24392695]
[82]
Hill, M.W.; Reddy, P.A.; Covey, D.F.; Rothman, S.M. Inhibition of voltage-dependent sodium channels by the anticonvulsant γ-aminobutyric acid type A receptor modulator, 3-benzyl-3-ethyl-2-piperidinone. J. Pharmacol. Exp. Ther., 1998, 285(3), 1303-1309.
[PMID: 9618437]
[83]
Lenkowski, P.W.; Ko, S.H.; Anderson, J.D.; Brown, M.L.; Patel, M.K. Block of human Nav1.5 sodium channels by novel α-hydroxyphenylamide analogues of phenytoin. Eur. J. Pharm. Sci., 2004, 21(5), 635-644.
[http://dx.doi.org/10.1016/j.ejps.2004.01.004] [PMID: 15066664]
[84]
Krivoshein, A.V.; Hess, G.P. Allosteric modulation of the GABAA receptor by phenobarbital and diethyl-lactam: A transient kinetic study. Proceedings of the 35th Annual Meeting of the Society for Neuroscience, Washington, DCNovember 12-16, 2005
[85]
Krivoshein, A.V.; Poreddy, A.R.; Covey, D.F.; Hess, G.P. Inhibition of the nicotinic acetylcholine receptor by α-substituted lactams: Relation to their antiepileptic effect. Proceedings of the 36th Annual Meeting of the Society for Neuroscience, Atlanta, GAOctober 14-18, 2006
[86]
Krivoshein, A.V.; Chen, Y.; Torres, J. Anticonvulsant drugs that inhibit the neuronal nAChR: Studies of enantiomerically pure 3-Me-3-Ph-pyrrolidine-2,5-dione and 2-Ph-butyramide. Proceedings of the 17th IUPAB International Biophysics Congress, Beijing, ChinaOctober 30 - November 3, 2011
[87]
Chen, Y.; Timofeeva, T.V.; Huang, J.; Ordonez, C.; Krivoshein, A.V. Methsuximide and N-desmethylmethsuximide: From crystal structures to pharmacological activity. Proceedings of the Neuroscience 2014 Meeting, Washington, DCNovember 15-19, 2014
[88]
Testa, E.; Fontanella, L.; Fava, F. Sostanze attive sul sistema nervoso centrale. Nota III – Azetidinoni 3,3-disostituiti. Farmaco, Sci., 1958, 13(2), 152-163.
[89]
Pfeiffer, C.C.; Stoughton, R.W.; Jenney, E.H. Physical constants and anticonvulsant effects of optical isomers of atrolactamide (Themisone) (M-144). Fed. Proc., 1954, 13, 394.
[90]
Meza-Toledo, S.E.; Ortega-González, C.; Juárez-Carvajal, E.; Carvajal-Sandoval, G. Stereoselective anticonvulsant activity of the enantiomers of (+/-)-2-hydroxy-2-phenylbutyramide. Arzneimittelforschung, 1995, 45(7), 756-759.
[PMID: 8573217]
[91]
Hovinga, C.A. Valrocemide (Teva/Acorda). Curr. Opin. Investig. Drugs, 2004, 5(1), 101-106.
[PMID: 14983982]
[92]
Bialer, M.; Johannessen, S.I.; Koepp, M.J.; Levy, R.H.; Perucca, E.; Tomson, T.; White, H.S. Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). I. Drugs in preclinical and early clinical development. Epilepsia, 2018, 59(10), 1811-1841.
[http://dx.doi.org/10.1111/epi.14557] [PMID: 30368792]
[93]
Bialer, M.; Johannessen, S.I.; Koepp, M.J.; Levy, R.H.; Perucca, E.; Tomson, T.; White, H.S. Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). II. Drugs in more advanced clinical development. Epilepsia, 2018, 59(10), 1842-1866.
[http://dx.doi.org/10.1111/epi.14555] [PMID: 30368788]


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VOLUME: 20
ISSUE: 2
Year: 2020
Published on: 09 May, 2020
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DOI: 10.2174/1871524920666200510005458
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