The glutamate hypothesis in ALS: Pathophysiology and drug development

Current Medicinal Chemistry

Volumn 21, Issue 31, 2014, Pages 3551-3575

  Blasco, H ^a,b   Mavel, S ^b   Corcia, P ^a,b   Gordon, P H ^c  

^a UNIVERSITY HOSPITAL OF TOURS   (France)

^b UNIVERSITÉ DE TOURS   (France)

^c Northern Navajo Medical Center   (United States)

Author keywords

Amyotrophic lateral sclerosis; Diagnosis; Glutamate; Neurodegeneration; Pathophysiology; Treatment

Indexed keywords

4 AMINOBUTYRIC ACID RECEPTOR; AMPA RECEPTOR; AMPA RECEPTOR ANTAGONIST; ANTICONVULSIVE AGENT; BIOLOGICAL MARKER; CALCIUM ION; CARBONATE DEHYDRATASE INHIBITOR; CEFTRIAXONE; DESIGNER DRUG; GABAPENTIN; GABAPENTIN ENACARBIL; GLUTAMATE RECEPTOR; GLUTAMATE RECEPTOR ANTAGONIST; GLUTAMATE TRANSPORTER; GLUTAMIC ACID; IONOTROPIC RECEPTOR; LAMOTRIGINE; MEMANTINE; MESSENGER RNA; METABOTROPIC RECEPTOR; NEUROPROTECTIVE AGENT; NEW DRUG; PLACEBO; PREGABALIN; RECEPTOR SUBTYPE; RILUZOLE; SEROTONIN 2C RECEPTOR; TALAMPANEL; TOPIRAMATE; UNINDEXED DRUG;

ADULT; AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL MODEL; ARTICLE; CHILD; CLINICAL TRIAL (TOPIC); DEGENERATIVE DISEASE; DIZZINESS; DRUG DESIGN; DRUG DOSE COMPARISON; DRUG DOSE INCREASE; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; DRUG STRUCTURE; DRUG TARGETING; EPILEPSY; HUMAN; MAJOR CLINICAL STUDY; MULTICENTER STUDY (TOPIC); NERVE CELL NECROSIS; NEUROLOGIC DISEASE; NEUROPHARMACOLOGY; NEUROTRANSMISSION; NEUROTRANSMITTER RELEASE; NONHUMAN; PATHOPHYSIOLOGY; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); QUANTITATIVE STRUCTURE ACTIVITY RELATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); TREATMENT OUTCOME; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG EFFECTS; GENETICS; METABOLISM; MOTONEURON; PATHOLOGY;

AMINO ACID TRANSPORT SYSTEM X-AG; AMYOTROPHIC LATERAL SCLEROSIS; GLUTAMIC ACID; HUMANS; MOTOR NEURONS; NEUROPROTECTIVE AGENTS; RECEPTORS, GLUTAMATE; RILUZOLE;

EID: 84925253060     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867321666140916120118     Document Type: Article

References (360)

1. Rowland, L.P.; Shneider, N.A. Amyotrophic lateral sclerosis. N. Engl. J. Med., 2001, 344(22), 1688-1700.
2. Logroscino, G.; Traynor, B.J.; Hardiman, O.; Chio, A.; Mitchell, D.; Swingler, R.J.; Millul, A.; Benn, E.; Beghi, E. Incidence of amyotrophic lateral sclerosis in Europe. J. Neurol. Neurosurg. Psychiatr., 2010, 81(4), 385-390.
3. Gordon, P.H.; Wang, Y.; Doorish, C.; Lewis, M.; Battista, V.; Mitsumoto, H.; Marder, K. A screening assessment of cognitive impairment in patients with ALS. Amyotroph. Lateral Scler., 2007, 8(6), 362-365.
4. Goetz, C.G. Chapter 15: Jean-Martin Charcot and the anatomo-clinical method of neurology. Handb. Clin. Neurol., 2010, 95, 203-212.
5. Gordon, P.H.; Cheng, B.; Katz, I.B.; Pinto, M.; Hays, A.P.; Mitsumoto, H.; Rowland, L.P. The natural history of primary lateral sclerosis. Neurology, 2006, 66(5), 647-653.
6. Sachs, C.; Conradi, S.; Kaijser, L. Autonomic function in amyotrophic lateral sclerosis: a study of cardiovascular responses. Acta Neurol. Scand., 1985, 71(5), 373-378.
7. Plaitakis, A.; Caroscio, J.T. Abnormal glutamate metabolism in amyotrophic lateral sclerosis. Ann. Neurol., 1987, 22(5), 575-579.
8. Rothstein, J.D.; Martin, L.J.; Kuncl, R.W. Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N. Engl. J. Med., 1992, 326(22), 1464-1468.
9. Roisen, F.J.; Bartfeld, H.; Donnenfeld, H.; Baxter, J. Neuron specific in vitro cytotoxicity of sera from patients with amyotrophic lateral sclerosis. Muscle Nerve, 1982, 5(1), 48-53.
10. Rothstein, J.D. Excitotoxic mechanisms in the pathogenesis of amyotrophic lateral sclerosis. Adv. Neurol., 1995, 68, 7-20; discussion 21-27.
11. Rothstein, J.D. Excitotoxicity and neurodegeneration in amyotrophic lateral sclerosis. Clin. Neurosci., 1995, 3(6), 348-359.
12. Lacomblez, L.; Bensimon, G.; Leigh, P.N.; Guillet, P.; Meininger, V. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet, 1996, 347(9013), 1425-1431.
13. Areosa, S.A.; Sherriff, F. Memantine for dementia. Cochrane Database Syst. Rev., 2003, 3, CD003154.
14. Gordon, P.H.; Meininger, V. How can we improve clinical trials in amyotrophic lateral sclerosis? Nat. Rev. Neurol., 2011, 7(11), 650-654.
15. Allen, N.J.; Barres, B.A. Signaling between glia and neurons: focus on synaptic plasticity. Curr. Opin. Neurobiol., 2005, 15(5), 542-548.
16. Fields, R.D.; Stevens-Graham, B. New insights into neuron-glia communication. Science, 2002, 298(5593), 556-562.
17. Rodriguez-Rodriguez, P.; Almeida, A.; Bolanos, J.P. Brain energy metabolism in glutamate-receptor activation and excitotoxicity: role for APC/C-Cdh1 in the balance glycolysis/pentose phosphate pathway. Neurochem. Int., 2013, 62(5), 750-756.
18. Hollmann, M.; Heinemann, S. Cloned glutamate receptors. Annu. Rev. Neurosci., 1994, 17, 31-108.
19. Bettler, B.; Mulle, C. Review: neurotransmitter receptors. II. AMPA and kainate receptors. Neuropharmacology, 1995, 34(2), 123-139.
20. Pin, J.P.; Gomeza, J.; Joly, C.; Bockaert, J. The metabotropic glutamate receptors: their second intracellular loop plays a critical role in the G-protein coupling specificity. Biochem. Soc. Trans., 1995, 23(1), 91-96.
21. Pin, J.P.; Duvoisin, R. The metabotropic glutamate receptors: structure and functions. Neuropharmacology, 1995, 34(1), 1-26.
22. Pin, J.P.; Bockaert, J. Get receptive to metabotropic glutamate receptors. Curr. Opin. Neurobiol., 1995, 5(3), 342-349.
23. Hume, R.I.; Dingledine, R.; Heinemann, S.F. Identification of a site in glutamate receptor subunits that controls calcium permeability. Science, 1991, 253(5023), 1028-1031.
24. Hollmann, M.; Hartley, M.; Heinemann, S. Ca2+ permeability of KA-AMPA-gated glutamate receptor channels depends on subunit composition. Science, 1991, 252(5007), 851-853.
25. Van Den Bosch, L.; Van Damme, P.; Bogaert, E.; Robberecht, W. The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis. Biochim. Biophys. Acta, 2006, 1762(11-12), 1068-1082.
26. Collingridge, G.L.; Lester, R.A. Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol. Rev., 1989, 41(2), 143-210.
27. Nicoll, R.A.; Malenka, R.C. Expression mechanisms underlying NMDA receptor-dependent long-term potentiation. Ann. N. Y. Acad. Sci., 1999, 868, 515-525.
28. Kutsuwada, T.; Kashiwabuchi, N.; Mori, H.; Sakimura, K.; Kushiya, E.; Araki, K.; Meguro, H.; Masaki, H.; Kumanishi, T.; Arakawa, M.; Mishina, M. Molecular diversity of the NMDA receptor channel. Nature, 1992, 358(6381), 36-41.
29. Monyer, H.; Burnashev, N.; Laurie, D.J.; Sakmann, B.; Seeburg, P.H. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron, 1994, 12(3), 529-540.
30. Kuner, T.; Wollmuth, L.P.; Karlin, A.; Seeburg, P.H.; Sakmann, B. Structure of the NMDA receptor channel M2 segment inferred from the accessibility of substituted cysteines. Neuron, 1996, 17(2), 343-352.
31. Lerma, J.; Marques, J.M. Kainate receptors in health and disease. Neuron, 2013, 80(2), 292-311.
32. Pizzi, M.; Benarese, M.; Boroni, F.; Goffi, F.; Valerio, A.; Spano, P.F. Neuroprotection by metabotropic glutamate receptor agonists on kainate-induced degeneration of motor neurons in spinal cord slices from adult rat. Neuropharmacology, 2000, 39(5), 903-910.
33. Anneser, J.M.; Horstmann, S.; Weydt, P.; Borasio, G.D. Activation of metabotropic glutamate receptors delays apoptosis of chick embryonic motor neurons in vitro. Neuroreport, 1998, 9(9), 2039-2043.
34. Tanaka, K.; Watase, K.; Manabe, T.; Yamada, K.; Watanabe, M.; Takahashi, K.; Iwama, H.; Nishikawa, T.; Ichihara, N.; Kikuchi, T.; Okuyama, S.; Kawashima, N.; Hori, S.; Takimoto, M.; Wada, K. Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science, 1997, 276(5319), 1699-702.
35. O'Kane, R.L.; Martinez-Lopez, I.; DeJoseph, M.R.; Vina, J.R.; Hawkins, R.A. Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood-brain barrier. A mechanism for glutamate removal. J. Biol. Chem., 1999, 274(45), 31891-31895.
36. Vacher, H.; Mohapatra, D.P.; Trimmer, J.S. Localization and targeting of voltage-dependent ion channels in mammalian central neurons. Physiol. Rev., 2008, 88(4), 1407-1447.
37. Kawahara, Y.; Ito, K.; Sun, H.; Ito, M.; Kanazawa, I.; Kwak, S. GluR4c, an alternative splicing isoform of GluR4, is abundantly expressed in the adult human brain. Brain Res. Mol. Brain Res., 2004, 127(1-2), 150-155.
38. Rothstein, J.D.; Van Kammen, M.; Levey, A.I.; Martin, L.J.; Kuncl, R.W. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann. Neurol., 1995, 38(1), 73-84.
39. Rothstein, J.D.; Dykes-Hoberg, M.; Pardo, C.A.; Bristol, L.A.; Jin, L.; Kuncl, R.W.; Kanai, Y.; Hediger, M.A.; Wang, Y.; Schielke, J.P.; Welty, D.F. Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron, 1996, 16(3), 675-686.
40. Bartels, C.; Mertens, N.; Hofer, S.; Merboldt, K.D.; Dietrich, J.; Frahm, J.; Ehrenreich, H. Callosal dysfunction in amyotrophic lateral sclerosis correlates with diffusion tensor imaging of the central motor system. Neuromuscul. Disord., 2008, 18(5), 398-407.
41. Trotti, D.; Rolfs, A.; Danbolt, N.C.; Brown, R.H., Jr.; Hediger, M.A. SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter. Nat. Neurosci., 1999, 2(9), 848.
42. Rothstein, J.D.; Patel, S.; Regan, M.R.; Haenggeli, C.; Huang, Y.H.; Bergles, D.E.; Jin, L.; Dykes Hoberg, M.; Vidensky, S.; Chung, D.S.; Toan, S.V.; Bruijn, L.I.; Su, Z.Z.; Gupta, P.; Fisher, P.B. Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature, 2005, 433(7021), 73-77.
43. Guo, H.; Lai, L.; Butchbach, M.E.; Stockinger, M.P.; Shan, X.; Bishop, G.A.; Lin, C.L. Increased expression of the glial glutamate transporter EAAT2 modulates excitotoxicity and delays the onset but not the outcome of ALS in mice. Hum. Mol. Genet., 2003, 12(19), 2519-2532.
44. Dunlop, J.; Beal McIlvain, H.; She, Y.; Howland, D.S. Impaired spinal cord glutamate transport capacity and reduced sensitivity to riluzole in a transgenic superoxide dismutase mutant rat model of amyotrophic lateral sclerosis. J. Neurosci., 2003, 23(5), 1688-1696.
45. Howland, D.S.; Liu, J.; She, Y.; Goad, B.; Maragakis, N.J.; Kim, B.; Erickson, J.; Kulik, J.; DeVito, L.; Psaltis, G.; DeGennaro, L.J.; Cleveland, D.W.; Rothstein, J.D. Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutantmediated amyotrophic lateral sclerosis (ALS). Proc. Natl. Acad. Sci. USA, 2002, 99(3), 1604-1609.
46. Bruijn, L.I.; Becher, M.W.; Lee, M.K.; Anderson, K.L.; Jenkins, N.A.; Copeland, N.G.; Sisodia, S.S.; Rothstein, J.D.; Borchelt, D.R.; Price, D.L.; Cleveland, D.W. ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron, 1997, 18(2), 327-338.
47. Giribaldi, F.; Milanese, M.; Bonifacino, T.; Anna Rossi, P.I.; Di Prisco, S.; Pittaluga, A.; Tacchetti, C.; Puliti, A.; Usai, C.; Bonanno, G. Group I metabotropic glutamate autoreceptors induce abnormal glutamate exocytosis in a mouse model of amyotrophic lateral sclerosis. Neuropharmacology, 2013, 66, 253-263.
48. Poulopoulou, C.; Davaki, P.; Koliaraki, V.; Kolovou, D.; Markakis, I.; Vassilopoulos, D. Reduced expression of metabotropic glutamate receptor 2mRNA in T cells of ALS patients. Ann. Neurol., 2005, 58(6), 946-949.
49. Aronica, E.; Catania, M.V.; Geurts, J.; Yankaya, B.; Troost, D. Immunohistochemical localization of group I and II metabotropic glutamate receptors in control and amyotrophic lateral sclerosis human spinal cord: upregulation in reactive astrocytes. Neuroscience, 2001, 105(2), 509-520.
50. Rossi, B.; Maton, G.; Collin, T. Calcium-permeable presynaptic AMPA receptors in cerebellar molecular layer interneurones. J. Physiol., 2008, 586(Pt 21), 5129-5145.
51. Cheah, B.C.; Kiernan, M.C. Dexpramipexole, the R(+) enantiomer of pramipexole, for the potential treatment of amyotrophic lateral sclerosis. IDrugs, 2010, 13(12), 911-920.
52. Rothstein, J.D.; Tsai, G.; Kuncl, R.W.; Clawson, L.; Cornblath, D.R.; Drachman, D.B.; Pestronk, A.; Stauch, B.L.; Coyle, J.T. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann. Neurol., 1990, 28(1), 18-25.
53. Shaw, P.J.; Forrest, V.; Ince, P.G.; Richardson, J.P.; Wastell, H.J. CSF and plasma amino acid levels in motor neuron disease: elevation of CSF glutamate in a subset of patients. Neurodegeneration, 1995, 4(2), 209-216.
54. Spreux-Varoquaux, O.; Bensimon, G.; Lacomblez, L.; Salachas, F.; Pradat, P.F.; Le Forestier, N.; Marouan, A.; Dib, M.; Meininger, V. Glutamate levels in cerebrospinal fluid in amyotrophic lateral sclerosis: a reappraisal using a new HPLC method with coulometric detection in a large cohort of patients. J. Neurol. Sci., 2002, 193(2), 73-78.
55. Gredal, O.; Moller, S.E. Effect of branched-chain amino acids on glutamate metabolism in amyotrophic lateral sclerosis. J. Neurol. Sci., 1995, 129(1), 40-43.
56. Ilzecka, J.; Stelmasiak, Z.; Solski, J.; Wawrzycki, S.; Szpetnar, M. Plasma amino acids concentration in amyotrophic lateral sclerosis patients. Amino Acids, 2003, 25(1), 69-73.
57. Perry, T.L.; Krieger, C.; Hansen, S.; Eisen, A. Amyotrophic lateral sclerosis: amino acid levels in plasma and cerebrospinal fluid. Ann. Neurol., 1990, 28(1), 12-17.
58. Wuolikainen, A.; Moritz, T.; Marklund, S.L.; Antti, H.; Andersen, P.M. Disease-related changes in the cerebrospinal fluid metabolome in amyotrophic lateral sclerosis detected by GC/TOFMS. PLoS One, 2011, 6(4), e17947.
59. Kumar, A.; Bala, L.; Kalita, J.; Misra, U.K.; Singh, R.L.; Khetrapal, C.L.; Babu, G.N. Metabolomic analysis of serum by (1) H NMR spectroscopy in amyotrophic lateral sclerosis. Clin. Chim. Acta, 2010, 411(7-8), 563-567.
60. Blasco, H.; Corcia, P.; Pradat, P.F.; Bocca, C.; Gordon, P.H.; Veyrat-Durebex, C.; Mavel, S.; Nadal-Desbarats, L.; Moreau, C.; Devos, D.; Andres, C.R.; Emond, P. Metabolomics in Cerebrospinal Fluid of Patients with Amyotrophic Lateral Sclerosis: An Untargeted Approach via High-Resolution Mass Spectrometry. J. Proteome Res., 2013, 12(8), 3746-3754.
61. Sasabe, J.; Miyoshi, Y.; Suzuki, M.; Mita, M.; Konno, R.; Matsuoka, M.; Hamase, K.; Aiso, S. D-amino acid oxidase controls motoneuron degeneration through D-serine. Proc. Natl. Acad. Sci. USA, 2012, 109(2), 627-632.
62. Sasabe, J.; Chiba, T.; Yamada, M.; Okamoto, K.; Nishimoto, I.; Matsuoka, M.; Aiso, S. D-serine is a key determinant of glutamate toxicity in amyotrophic lateral sclerosis. EMBO J., 2007, 26(18), 4149-4159.
63. Mitchell, J.; Paul, P.; Chen, H.J.; Morris, A.; Payling, M.; Falchi, M.; Habgood, J.; Panoutsou, S.; Winkler, S.; Tisato, V.; Hajitou, A.; Smith, B.; Vance, C.; Shaw, C.; Mazarakis, N.D.; de Belleroche, J. Familial amyotrophic lateral sclerosis is associated with a mutation in D-amino acid oxidase. Proc. Natl. Acad. Sci. USA, 2010, 107(16), 7556-7561.
64. Lipton, S.A.; Rosenberg, P.A. Excitatory amino acids as a final common pathway for neurologic disorders. N. Engl. J. Med., 1994, 330(9), 613-622.
65. Tapia, R.; Medina-Ceja, L.; Pena, F. On the relationship between extracellular glutamate, hyperexcitation and neurodegeneration, in vivo. Neurochem. Int., 1999, 34(1), 23-31.
66. Meldrum, B.S. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J. Nutr., 2000, 130(4S Suppl), 1007S-1015S.
67. Grosskreutz, J.; Van Den Bosch, L.; Keller, B.U. Calcium dysregulation in amyotrophic lateral sclerosis. Cell Calcium., 2010, 47(2), 165-174.
68. Scott, S.; Kranz, J.E.; Cole, J.; Lincecum, J.M.; Thompson, K.; Kelly, N.; Bostrom, A.; Theodoss, J.; Al-Nakhala, B.M.; Vieira, F.G.; Ramasubbu, J.; Heywood, J.A. Design, power, and interpretation of studies in the standard murine model of ALS. Amyotroph. Lateral. Scler., 2008, 9(1), 4-15.
69. Gordon, P.H. Amyotrophic Lateral Sclerosis: An update for 2013 Clinical Features, Pathophysiology, Management and Therapeutic Trials. Aging Dis., 2013, 4(5), 295-310.
70. Mitsumoto, H.; Gordon, P.; Kaufmann, P.; Gooch, C.L.; Przedborski, S.; Rowland, L.P. Randomized control trials in ALS: lessons learned. Amyotroph. Lateral. Scler. Other Motor. Neuron. Disord., 2004, 5 Suppl 1, 8-13.
71. Buckingham, S.D.; Kwak, S.; Jones, A.K.; Blackshaw, S.E.; Sattelle, D.B. Edited GluR2, a gatekeeper for motor neurone survival? Bioessays, 2008, 30(11-12), 1185-1192.
72. Barrie, E.S.; Smith, R.M.; Sanford, J.C.; Sadee, W. mRNA transcript diversity creates new opportunities for pharmacological intervention. Mol. Pharmacol., 2012, 81(5), 620-630.
73. Jarmin, S.; Kymalainen, H.; Popplewell, L.; Dickson, G. New developments in the use of gene therapy to treat Duchenne muscular dystrophy. Expert Opin. Biol. Ther., 2014, 14(2), 209-230.
74. Streit, A.K.; Decher, N. A-to-I RNA editing modulates the pharmacology of neuronal ion channels and receptors. Biochem. (Mosc.), 2011, 76(8), 890-899.
75. Werry, T.D.; Loiacono, R.; Sexton, P.M.; Christopoulos, A. RNA editing of the serotonin 5HT2C receptor and its effects on cell signalling, pharmacology and brain function. Pharmacol. Ther., 2008, 119(1), 7-23.
76. Durrant, J.D.; McCammon, J.A. Towards the development of novel Trypanosoma brucei RNA editing ligase 1 inhibitors. BMC Pharmacol., 2011, 11, 9.
77. Durrant, J.D.; Hall, L.; Swift, R.V.; Landon, M.; Schnaufer, A.; Amaro, R.E. Novel naphthalene-based inhibitors of Trypanosoma brucei RNA editing ligase 1. PLoS. Negl. Trop. Dis., 2010, 4(8), e803.
78. Sawada, J.; Yamashita, T.; Aizawa, H.; Aburakawa, Y.; Hasebe, N.; Kwak, S. Effects of antidepressants on GluR2 Q/R site-RNA editing in modified HeLa cell line. Neurosci. Res., 2009, 64(3), 251-258.
79. Collingridge, G.L.; Singer, W. Excitatory amino acid receptors and synaptic plasticity. Trends Pharmacol. Sci., 1990, 11(7), 290-296.
80. Danysz, W.; Zajaczkowski, W.; Parsons, C.G. Modulation of learning processes by ionotropic glutamate receptor ligands. Behav. Pharmacol., 1995, 6(5 And 6), 455-474.
81. Colton, C.K.; Kong, Q.; Lai, L.; Zhu, M.X.; Seyb, K.I.; Cuny, G.D.; Xian, J.; Glicksman, M.A.; Lin, C.L. Identification of translational activators of glial glutamate transporter EAAT2 through cell-based high-throughput screening: an approach to prevent excitotoxicity. J. Biomol. Screen., 2010, 15(6), 653-662.
82. Mao, J. Glutamate transporter: an unexpected target for some antibiotics. Mol. Pain., 2005, 1, 5.
83. Fontana, A.C.; de Oliveira Beleboni, R.; Wojewodzic, M.W.; Ferreira Dos Santos, W.; Coutinho-Netto, J.; Grutle, N.J.; Watts, S.D.; Danbolt, N.C.; Amara, S.G. Enhancing glutamate transport: mechanism of action of Parawixin1, a neuroprotective compound from Parawixia bistriata spider venom. Mol. Pharmacol., 2007, 72(5), 1228-1237.
84. Torres-Salazar, D.; Fahlke, C. Parawixin1: a spider toxin opening new avenues for glutamate transporter pharmacology. Mol. Pharmacol., 2007, 72(5), 1100-1102.
85. Xing, X.; Chang, L.C.; Kong, Q.; Colton, C.K.; Lai, L.; Glicksman, M.A.; Lin, C.L.; Cuny, G.D. Structure-activity relationship study of pyridazine derivatives as glutamate transporter EAAT2 activators. Bioorg. Med. Chem. Lett., 2011, 21(19), 5774-5777.
86. Lin, C.L.; Kong, Q.; Cuny, G.D.; Glicksman, M.A. Glutamate transporter EAAT2: a new target for the treatment of neurodegenerative diseases. Future Med. Chem., 2012, 4(13), 1689-1700.
87. Luethi, E.; Nguyen, K.T.; Burzle, M.; Blum, L.C.; Suzuki, Y.; Hediger, M.; Reymond, J.L. Identification of selective norbornane-type aspartate analogue inhibitors of the glutamate transporter 1 (GLT-1) from the chemical universe generated database (GDB). J. Med. Chem., 2010, 53(19), 7236-7250.
88. Wu, J.; Lee, M.R.; Choi, S.; Kim, T.; Choi, D.S. ENT1 regulates ethanol-sensitive EAAT2 expression and function in astrocytes. Alcohol Clin. Exp. Res., 2010, 34(6), 1110-1117.
89. Bunch, L.; Gefflaut, T.; Alaux, S.; Sagot, E.; Nielsen, B.; Pickering, D.S. Pharmacological characterization of (4R)-alkyl glutamate analogues at the ionotropic glutamate receptors-focus on subtypes iGlu(5-7). Eur. J. Pharmacol., 2009, 609(1-3), 1-4.
90. Alaux, S.; Kusk, M.; Sagot, E.; Bolte, J.; Jensen, A.A.; BraunerOsborne, H.; Gefflaut, T.; Bunch, L. Chemoenzymatic synthesis of a series of 4-substituted glutamate analogues and pharmacological characterization at human glutamate transporters subtypes 1-3. J. Med. Chem., 2005, 48(25), 7980-7992.
91. Sagot, E.; Pickering, D.S.; Pu, X.; Umberti, M.; Stensbol, T.B.; Nielsen, B.; Chapelet, M.; Bolte, J.; Gefflaut, T.; Bunch, L. Chemo-enzymatic synthesis of a series of 2,4-syn-functionalized (S)-glutamate analogues: new insight into the structure-activity relation of ionotropic glutamate receptor subtypes 5, 6, and 7. J. Med. Chem., 2008, 51(14), 4093-4103.
92. Assaf, Z.; Larsen, A.P.; Venskutonyte, R.; Han, L.; Abrahamsen, B.; Nielsen, B.; Gajhede, M.; Kastrup, J.S.; Jensen, A.A.; Pickering, D.S.; Frydenvang, K.; Gefflaut, T.; Bunch, L. Chemoenzymatic synthesis of new 2,4-syn-functionalized (S)-glutamate analogues and structure-activity relationship studies at ionotropic glutamate receptors and excitatory amino acid transporters. J. Med. Chem., 2013, 56(4), 1614-1628.
93. Bunch, L.; Pickering, D.S.; Gefflaut, T.; Vinatier, V.; Helaine, V.; Amir, A.; Nielsen, B.; Jensen, A.A. 4,4-Dimethyl- and diastereomeric 4-hydroxy-4-methyl- (2S)-glutamate analogues display distinct pharmacological profiles at ionotropic glutamate receptors and excitatory amino acid transporters. ChemMedChem, 2009, 4(11), 1925-1929.
94. Bensimon, G.; Ludolph, A.; Agid, Y.; Vidailhet, M.; Payan, C.; Leigh, P.N. Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study. Brain, 2009, 132(Pt 1), 156-171.
95. Pittenger, C.; Coric, V.; Banasr, M.; Bloch, M.; Krystal, J.H.; Sanacora, G. Riluzole in the treatment of mood and anxiety disorders. CNS Drugs, 2008, 22(9), 761-786.
96. Doble, A. The pharmacology and mechanism of action of riluzole. Neurology, 1996, 47(6 Suppl 4), S233-241.
97. Bensimon, G.; Lacomblez, L.; Meininger, V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N. Engl. J. Med., 1994, 330(9), 585-591.
98. Jimonet, P.; Audiau, F.; Barreau, M.; Blanchard, J.C.; Boireau, A.; Bour, Y.; Coleno, M.A.; Doble, A.; Doerflinger, G.; Huu, C.D.; Donat, M.H.; Duchesne, J.M.; Ganil, P.; Gueremy, C.; Honor, E.; Just, B.; Kerphirique, R.; Gontier, S.; Hubert, P.; Laduron, P.M.; Le Blevec, J.; Meunier, M.; Miquet, J.M.; Nemecek, C.; Pasquet, M.; Piot, O.; Pratt, J.; Rataud, J.; Reibaud, M.; Stutzmann, J.M.; Mignani, S. Riluzole series. Synthesis and in vivo "antiglutamate" activity of 6-substituted-2-benzothiazolamines and 3-substituted-2-imino-benzothiazolines. J. Med. Chem., 1999, 42(15), 2828-2843.
99. Jimonet, P.; Barreau, M.; Blanchard, J.C.; Boireau, A.; Doble, A.; Laduron, P.; Lavayre, J.; Malgouris, C.; Piot, O.; Pratt, J.; Rataud, J.; Reibaud, M.; Mignani, S.; Stutzmann, J.-M. Synthesis, anticonvulsant and neuroprotective activities of RP 66055, a riluzole derivative. Bioorg. Med. Chem., 1994, 2(8), 793-798.
100. Knox, C.; Law, V.; Jewison, T.; Liu, P.; Ly, S.; Frolkis, A.; Pon, A.; Banco, K.; Mak, C.; Neveu, V.; Djoumbou, Y.; Eisner, R.; Guo, A.C.; Wishart, D.S. DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic. Acids Res., 2011, 39(Database issue), D1035-1041.
101. Sierra Bello, O.; Gonzalez, J.; Capani, F.; Barreto, G.E. In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: implications for amyotrophic lateral sclerosis therapy. J. Theor. Biol., 2012, 315, 53-63.
102. Miloushev, V.Z.; Levine, J.A.; Arbing, M.A.; Hunt, J.F.; Pitt, G.S.; Palmer, A.G. 3rd, Solution structure of the NaV1.2 C-terminal EF-hand domain. J. Biol. Chem., 2009, 284(10), 6446-6454.
103. Sanderink, G.J.; Bournique, B.; Stevens, J.; Petry, M.; Martinet, M. Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. J. Pharmacol. Exp. Ther., 1997, 282(3), 1465-1472.
104. Groeneveld, G.J.; Veldink, J.H.; van der Tweel, I.; Kalmijn, S.; Beijer, C.; de Visser, M.; Wokke, J.H.; Franssen, H.; van den Berg, L.H. A randomized sequential trial of creatine in amyotrophic lateral sclerosis. Ann. Neurol., 2003, 53(4), 437-445.
105. McDonnell, M.E.; Vera, M.D.; Blass, B.E.; Pelletier, J.C.; King, R.C.; Fernandez-Metzler, C.; Smith, G.R.; Wrobel, J.; Chen, S.; Wall, B.A.; Reitz, A.B. Riluzole prodrugs for melanoma and ALS: design, synthesis, and in vitro metabolic profiling. Bioorg. Med. Chem., 2012, 20(18), 5642-5648.
106. Hassan, M.Z.; Khan, S.A.; Amir, M. Design, synthesis and evaluation of N-(substituted benzothiazol-2-yl)amides as anticonvulsant and neuroprotective. Eur. J. Med. Chem., 2012, 58, 206-213.
107. Amnerkar, N.D.; Bhusari, K.P. Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and 1-acetyl-pyrazolin derivatives of aminobenzothiazole. Eur. J. Med. Chem., 2010, 45(1), 149-159.
108. Wu, Y.; Satkunendrarajah, K.; Teng, Y.; Chow, D.S.; Buttigieg, J.; Fehlings, M.G. Delayed post-injury administration of riluzole is neuroprotective in a preclinical rodent model of cervical spinal cord injury. J. Neurotrauma, 2013, 30(6), 441-452.
109. Milane, A.; Tortolano, L.; Fernandez, C.; Bensimon, G.; Meininger, V.; Farinotti, R. Brain and plasma riluzole pharmacokinetics: effect of minocycline combination. J. Pharm. Pharm. Sci., 2009, 12(2), 209-217.
110. Milane, A.; Fernandez, C.; Vautier, S.; Bensimon, G.; Meininger, V.; Farinotti, R. Minocycline and riluzole brain disposition: interactions with p-glycoprotein at the blood-brain barrier. J. Neurochem., 2007, 103(1), 164-173.
111. Maltese, A.; Maugeri, F.; Drago, F.; Bucolo, C. Simple determination of riluzole in rat brain by high-performance liquid chromatography and spectrophotometric detection. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci., 2005, 817(2), 331-334.
112. Colovic, M.; Zennaro, E.; Caccia, S. Liquid chromatographic assay for riluzole in mouse plasma and central nervous system tissues. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci., 2004, 803(2), 305-309.
113. Bruno, R.; Vivier, N.; Montay, G.; Le Liboux, A.; Powe, L.K.; Delumeau, J.C.; Rhodes, G.R. Population pharmacokinetics of riluzole in patients with amyotrophic lateral sclerosis. Clin. Pharmacol. Ther., 1997, 62(5), 518-526.
114. Chow, D.S.; Teng, Y.; Toups, E.G.; Aarabi, B.; Harrop, J.S.; Shaffrey, C.I.; Johnson, M.M.; Boakye, M.; Frankowski, R.F.; Fehlings, M.G.; Grossman, R.G. Pharmacology of riluzole in acute spinal cord injury. J. Neurosurg. Spine, 2012, 17(1 Suppl), 129-140.
115. Frizzo, M.E.; Dall'Onder, L.P.; Dalcin, K.B.; Souza, D.O. Riluzole enhances glutamate uptake in rat astrocyte cultures. Cell. Mol. Neurobiol., 2004, 24(1), 123-128.
116. Azbill, R.D.; Mu, X.; Springer, J.E. Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes. Brain Res., 2000, 871(2), 175-180.
117. Cheah, B.C.; Vucic, S.; Krishnan, A.V.; Kiernan, M.C. Riluzole, neuroprotection and amyotrophic lateral sclerosis. Curr. Med. Chem., 2010, 17(18), 1942-1199.
118. Bellingham, M.C. A review of the neural mechanisms of action and clinical efficiency of riluzole in treating amyotrophic lateral sclerosis: what have we learned in the last decade? CNS Neurosci. Ther., 2011, 17(1), 4-31.
119. Prakriya, M.; Mennerick, S. Selective depression of low-release probability excitatory synapses by sodium channel blockers. Neuron, 2000, 26(3), 671-682.
120. Lamanauskas, N.; Nistri, A. Riluzole blocks persistent Na+ and Ca2+ currents and modulates release of glutamate via presynaptic NMDA receptors on neonatal rat hypoglossal motoneurons in vitro. Eur. J. Neurosci., 2008, 27(10), 2501-2514.
121. He, Y.; Zorumski, C.F.; Mennerick, S. Contribution of presynaptic Na(+) channel inactivation to paired-pulse synaptic depression in cultured hippocampal neurons. J. Neurophysiol., 2002, 87(2), 925-936.
122. Centonze, D.; Calabresi, P.; Pisani, A.; Marinelli, S.; Marfia, G.A.; Bernardi, G. Electrophysiology of the neuroprotective agent riluzole on striatal spiny neurons. Neuropharmacology, 1998, 37(8), 1063-1070.
123. Benavides, J.; Camelin, J.C.; Mitrani, N.; Flamand, F.; Uzan, A.; Legrand, J.J.; Gueremy, C.; Le Fur, G. 2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission-II. Biochemical properties. Neuropharmacology, 1985, 24(11), 1085-1092.
124. Urbani, A.; Belluzzi, O. Riluzole inhibits the persistent sodium current in mammalian CNS neurons. Eur. J. Neurosci., 2000, 12(10), 3567-3574.
125. van Zundert, B.; Peuscher, M.H.; Hynynen, M.; Chen, A.; Neve, R.L.; Brown, R.H., Jr.; Constantine-Paton, M.; Bellingham, M.C. Neonatal neuronal circuitry shows hyperexcitable disturbance in a mouse model of the adult-onset neurodegenerative disease amyotrophic lateral sclerosis. J. Neurosci., 2008, 28(43), 10864-10874.
126. Kuo, J.J.; Lee, R.H.; Zhang, L.; Heckman, C.J. Essential role of the persistent sodium current in spike initiation during slowly rising inputs in mouse spinal neurones. J. Physiol., 2006, 574(Pt 3), 819-834.
127. Cao, Y.J.; Dreixler, J.C.; Couey, J.J.; Houamed, K.M. Modulation of recombinant and native neuronal SK channels by the neuroprotective drug riluzole. Eur. J. Pharmacol., 2002, 449(1-2), 47-54.
128. Dimitriadi, M.; Kye, M.J.; Kalloo, G.; Yersak, J.M.; Sahin, M.; Hart, A.C. The neuroprotective drug riluzole acts via small conductance Ca2+-activated K+ channels to ameliorate defects in spinal muscular atrophy models. J. Neurosci., 2013, 33(15), 6557-6562.
129. Huang, F.; Gallo, V. Gene structure of the rat kainate receptor subunit KA2 and characterization of an intronic negative regulatory region. J. Biol. Chem., 1997, 272(13), 8618-8627.
130. Hubert, J.P.; Burgevin, M.C.; Terro, F.; Hugon, J.; Doble, A. Effects of depolarizing stimuli on calcium homeostasis in cultured rat motoneurones. Br. J. Pharmacol., 1998, 125(7), 1421-1428.
131. Vucic, S.; Lin, C.S.; Cheah, B.C.; Murray, J.; Menon, P.; Krishnan, A.V.; Kiernan, M.C. Riluzole exerts central and peripheral modulating effects in amyotrophic lateral sclerosis. Brain, 2013, 136(Pt 5), 1361-1370.
132. MacIver, M.B.; Amagasu, S.M.; Mikulec, A.A.; Monroe, F.A. Riluzole anesthesia: use-dependent block of presynaptic glutamate fibers. Anesthesiology, 1996, 85(3), 626-634.
133. Pace, R.W.; Mackay, D.D.; Feldman, J.L.; Del Negro, C.A. Role of persistent sodium current in mouse preBotzinger Complex neurons and respiratory rhythm generation. J. Physiol., 2007, 580(Pt. 2), 485-496.
134. Rammes, G.; Zieglgansberger, W.; Parsons, C.G. The fraction of activated N-methyl-D-aspartate receptors during synaptic transmission remains constant in the presence of the glutamate release inhibitor riluzole. J. Neural. Transm., 2008, 115(8), 1119-1126.
135. Tazerart, S.; Viemari, J.C.; Darbon, P.; Vinay, L.; Brocard, F. Contribution of persistent sodium current to locomotor pattern generation in neonatal rats. J. Neurophysiol., 2007, 98(2), 613-628.
136. Bellingham, M.C. Pre- and postsynaptic mechanisms underlying inhibition of hypoglossal motor neuron excitability by riluzole. J. Neurophysiol., 2013, 110(5), 1047-1061.
137. Du, J.; Suzuki, K.; Wei, Y.; Wang, Y.; Blumenthal, R.; Chen, Z.; Falke, C.; Zarate, C.A., Jr.; Manji, H.K. The anticonvulsants lamotrigine, riluzole, and valproate differentially regulate AMPA receptor membrane localization: relationship to clinical effects in mood disorders. Neuropsychopharmacology, 2007, 32(4), 793-802.
138. Hubert, J.P.; Delumeau, J.C.; Glowinski, J.; Premont, J.; Doble, A. Antagonism by riluzole of entry of calcium evoked by NMDA and veratridine in rat cultured granule cells: evidence for a dual mechanism of action. Br. J. Pharmacol., 1994, 113(1), 261-267.
139. Noh, K.M.; Hwang, J.Y.; Shin, H.C.; Koh, J.Y. A novel neuroprotective mechanism of riluzole: direct inhibition of protein kinase C. Neurobiol. Dis., 2000, 7(4), 375-383.
140. Rothstein, J.D. Therapeutic horizons for amyotrophic lateral sclerosis. Curr. Opin. Neurobiol., 1996, 6(5), 679-687.
141. Fumagalli, E.; Funicello, M.; Rauen, T.; Gobbi, M.; Mennini, T. Riluzole enhances the activity of glutamate transporters GLAST, GLT1 and EAAC1. Eur. J. Pharmacol., 2008, 578(2-3), 171-176.
142. Carbone, M.; Duty, S.; Rattray, M. Riluzole elevates GLT-1 activity and levels in striatal astrocytes. Neurochem. Int., 2012, 60(1), 31-38.
143. Dall'Igna, O.P.; Bobermin, L.D.; Souza, D.O.; Quincozes-Santos, A. Riluzole increases glutamate uptake by cultured C6 astroglial cells. Int. J. Dev. Neurosci., 2013, 31(7), 482-486.
144. Richter, J.M.; Schaefer, M.; Hill, K. Riluzole activates TRPC5 channels independently of PLC activity. Br. J. Pharmacol., 2014, 171(1), 158-170.
145. Daniel, B.; Green, O.; Viskind, O.; Gruzman, A. Riluzole increases the rate of glucose transport in L6 myotubes and NSC-34 motor neuron-like cells via AMPK pathway activation. Amyotroph. Lateral. Scler. Frontotemporal. Degener., 2013, 14(5-6), 434-443.
146. Bonnefont-Rousselot, D.; Lacomblez, L.; Jaudon, M.; Lepage, S.; Salachas, F.; Bensimon, G.; Bizard, C.; Doppler, V.; Delattre, J.; Meininger, V. Blood oxidative stress in amyotrophic lateral sclerosis. J. Neurol. Sci., 2000, 178(1), 57-62.
147. Rinwa, P.; Jaggi, A.S.; Singh, N. Pharmacological investigation of memory restorative effect of riluzole in mice. Indian J. Pharmacol., 2012, 44(3), 366-371.
148. Gottfried, C.; Tramontina, F.; Goncalves, D.; Goncalves, C.A.; Moriguchi, E.; Dias, R.D.; Wofchuk, S.T.; Souza, D.O. Glutamate uptake in cultured astrocytes depends on age: a study about the effect of guanosine and the sensitivity to oxidative stress induced by H(2)O(2). Mech. Ageing Dev., 2002, 123(10), 1333-1340.
149. Mehta, A.; Prabhakar, M.; Kumar, P.; Deshmukh, R.; Sharma, P.L. Excitotoxicity: bridge to various triggers in neurodegenerative disorders. Eur. J. Pharmacol., 2013, 698(1-3), 6-18.
150. Trotti, D.; Danbolt, N.C.; Volterra, A. Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration? Trends Pharmacol. Sci., 1998, 19, (8), 328-334.
151. Jahn, K.; Schlesinger, F.; Jin, L.J.; Dengler, R.; Bufler, J.; Krampfl, K. Molecular mechanisms of interaction between the neuroprotective substance riluzole and GABA(A)-receptors. Naunyn. Schmiedebergs Arch. Pharmacol., 2008, 378(1), 53-63.
152. Miller, R.G.; Mitchell, J.D.; Lyon, M.; Moore, D.H. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst. Rev., 2002(2), CD001447.
153. Lacomblez, L.; Bensimon, G.; Leigh, P.N.; Debove, C.; Bejuit, R.; Truffinet, P.; Meininger, V. Long-term safety of riluzole in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Other Motor. Neuron. Disord., 2002, 3(1), 23-29.
154. Taylor, C.P. Mechanisms of new antiepileptic drugs. Adv. Neurol., 1999, 79, 1011-1026.
155. Andrews, C.O.; Fischer, J.H. Gabapentin: a new agent for the management of epilepsy. Ann. Pharmacother., 1994, 28(10), 1188-1196.
156. Marson, A.G.; Kadir, Z.A.; Chadwick, D.W. New antiepileptic drugs: a systematic review of their efficacy and tolerability. BMJ, 1996, 313(7066), 1169-1174.
157. Beydoun, A. Monotherapy trials of new antiepileptic drugs. Epilepsia, 1997, 38 Suppl 9, S21-31.
158. Taylor, C.P.; Gee, N.S.; Su, T.Z.; Kocsis, J.D.; Welty, D.F.; Brown, J.P.; Dooley, D.J.; Boden, P.; Singh, L. A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res., 1998, 29(3), 233-249.
159. Taylor, C.P.; Angelotti, T.; Fauman, E. Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res., 2007, 73(2), 137-150.
160. Satzinger, G. Antiepileptics from gamma-aminobutyric acid. Arzneimittelforschung, 1994, 44(3), 261-266.
161. Lebedyeva, I.O.; Ostrov, D.A.; Neubert, J.; Steel, P.J.; Patel, K.; Sileno, S.M.; Goncalves, K.; Ibrahim, M.A.; Alamry, K.A.; Katritzky, A.R. Gabapentin hybrid peptides and bioconjugates. Bioorg. Med. Chem., 2014, 22(4), 1479-1486.
162. Blakemore, D.C.; Bryans, J.S.; Carnell, P.; Chessum, N.E.; Field, M.J.; Kinsella, N.; Kinsora, J.K.; Osborne, S.A.; Williams, S.C. Synthesis and in vivo evaluation of 3-substituted gababutins. Bioorg. Med. Chem. Lett., 2010, 20(1), 362-365.
163. Catarzi, D.; Colotta, V.; Varano, F. Competitive AMPA receptor antagonists. Med. Res. Rev., 2007, 27(2), 239-278.
164. Kaufmann, P.; Lomen-Hoerth, C. ALS treatment strikes out while trying for a homer: the topiramate trial. Neurology, 2003, 61(4), 434-435.
165. Rogawski, M.A.; Loscher, W. The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions. Nat. Med., 2004, 10(7), 685-692.
166. Schlicker, E.; Reimann, W.; Gothert, M. Gabapentin decreases monoamine release without affecting acetylcholine release in the brain. Arzneimittelforsch, 1985, 35(9), 1347-1349.
167. McLean, M.J. Clinical pharmacokinetics of gabapentin. Neurology, 1994, 44(6 Suppl 5), S17-S22; discussion S31-12.
168. Welty, D.F.; Schielke, G.P.; Rothstein, J.D. Potential treatment of amyotrophic lateral sclerosis with gabapentin: a hypothesis. Ann. Pharmacother., 1995, 29(11), 1164-1167.
169. Goldlust, A.; Su, T.Z.; Welty, D.F.; Taylor, C.P.; Oxender, D.L. Effects of anticonvulsant drug gabapentin on the enzymes in metabolic pathways of glutamate and GABA. Epilepsy Res., 1995, 22(1), 1-11.
170. Hutson, S.M.; Berkich, D.; Drown, P.; Xu, B.; Aschner, M.; LaNoue, K.F. Role of branched-chain aminotransferase isoenzymes and gabapentin in neurotransmitter metabolism. J. Neurochem., 1998, 71(2), 863-874.
171. Rothstein, J.D.; Kuncl, R.W. Neuroprotective strategies in a model of chronic glutamate-mediated motor neuron toxicity. J. Neurochem., 1995, 65(2), 643-651.
172. Gurney, M.E.; Cutting, F.B.; Zhai, P.; Doble, A.; Taylor, C.P.; Andrus, P.K.; Hall, E.D. Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis. Ann. Neurol., 1996, 39(2), 147-157.
173. Kalra, S.; Cashman, N.R.; Caramanos, Z.; Genge, A.; Arnold, D.L. Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy. AJNR Am. J. Neuroradiol., 2003, 24(3), 476-480.
174. Miller, R.G.; Moore, D.; Young, L.A.; Armon, C.; Barohn, R.J.; Bromberg, M.B.; Bryan, W.W.; Gelinas, D.F.; Mendoza, M.C.; Neville, H.E.; Parry, G.J.; Petajan, J.H.; Ravits, J.M.; Ringel, S.P.; Ross, M.A. Placebo-controlled trial of gabapentin in patients with amyotrophic lateral sclerosis. WALS Study Group. Western Amyotrophic Lateral Sclerosis Study Group. Neurology, 1996, 47(6), 1383-1388.
175. Miller, R.G.; Moore, D.H., 2nd; Gelinas, D.F.; Dronsky, V.; Mendoza, M.; Barohn, R.J.; Bryan, W.; Ravits, J.; Yuen, E.; Neville, H.; Ringel, S.; Bromberg, M.; Petajan, J.; Amato, A.A.; Jackson, C.; Johnson, W.; Mandler, R.; Bosch, P.; Smith, B.; Graves, M.; Ross, M.; Sorenson, E.J.; Kelkar, P.; Parry, G.; Olney, R. Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis. Neurology, 2001, 56(7), 843-848.
176. Gordon, P.H. The murky path to drug discovery in ALS becomes clearer. Lancet Neurol., 2013, 12(11), 1037-1038.
177. Shank, R.P.; Gardocki, J.F.; Streeter, A.J.; Maryanoff, B.E. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia, 2000, 41 Suppl 1, S3-9.
178. Sachdeo, R.C.; Glauser, T.A.; Ritter, F.; Reife, R.; Lim, P.; Pledger, G. A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group. Neurology, 1999, 52(9), 1882-1887.
179. Silberstein, S.D. Topiramate in migraine prevention: evidence-based medicine from clinical trials. Neurol. Sci., 2004, 25 Suppl 3, S244-245.
180. White, H.S. Molecular pharmacology of topiramate: managing seizures and preventing migraine. Headache, 2005, 45 Suppl 1, S48-56.
181. 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 Eigth Eilat Conference (EILAT VIII). Epilepsy Res., 2007, 73(1), 1-52.
182. Tiihonen, J.; Halonen, P.; Wahlbeck, K.; Repo-Tiihonen, E.; Hyvarinen, S.; Eronen, M.; Putkonen, H.; Takala, P.; Mehtonen, O.P.; Puck, M.; Oksanen, J.; Koskelainen, P.; Joffe, G.; Aer, J.; Hallikainen, T.; Ryynanen, O.P.; Tupala, E. Topiramate add-on in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial. J. Clin. Psychiatry, 2005, 66(8), 1012-1015.
183. Van Ameringen, M.; Mancini, C.; Pipe, B.; Oakman, J.; Bennett, M. An open trial of topiramate in the treatment of generalized social phobia. J. Clin. Psychiatry, 2004, 65(12), 1674-1678.
184. Bartolini, M.; Silvestrini, M.; Taffi, R.; Lanciotti, C.; Luconi, R.; Capecci, M.; Provinciali, L. Efficacy of topiramate and valproate in chronic migraine. Clin. Neuropharmacol., 2005, 28(6), 277-279.
185. McIntyre, R.S.; Riccardelli, R.; Binder, C.; Kusumakar, V. Open-label adjunctive topiramate in the treatment of unstable bipolar disorder. Can. J. Psychiatry, 2005, 50(7), 415-422.
186. Landmark, C.J.; Rytter, E.; Johannessen, S.I. Clinical use of antiepileptic drugs at a referral centre for epilepsy. Seizure, 2007, 16(4), 356-364.
187. Winum, J.Y.; Scozzafava, A.; Montero, J.L.; Supuran, C.T. Metal binding functions in the design of carbonic anhydrase inhibitors. Curr. Top. Med. Chem., 2007, 7(9), 835-848.
188. Ghiasi, P.; Hosseinkhani, S.; Noori, A.; Nafissi, S.; Khajeh, K. Mitochondrial complex I deficiency and ATP/ADP ratio in lymphocytes of amyotrophic lateral sclerosis patients. Neurol. Res., 2012, 34(3), 297-303.
189. Thiry, A.; Dogne, J.M.; Supuran, C.T.; Masereel, B. Carbonic anhydrase inhibitors as anticonvulsant agents. Curr. Top. Med. Chem., 2007, 7(9), 855-864.
190. Maryanoff, B.E.; Costanzo, M.J.; Nortey, S.O.; Greco, M.N.; Shank, R.P.; Schupsky, J.J.; Ortegon, M.P.; Vaught, J.L. Structure-activity studies on anticonvulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives. J. Med. Chem., 1998, 41(8), 1315-1343.
191. Aggarwal, M.; Kondeti, B.; McKenna, R. Anticonvulsant/ antiepileptic carbonic anhydrase inhibitors: a patent review. Expert Opin. Ther. Pat., 2013, 23(6), 717-724.
192. Brorson, J.R.; Manzolillo, P.A.; Miller, R.J. Ca2+ entry via AMPA/KA receptors and excitotoxicity in cultured cerebellar Purkinje cells. J. Neurosci., 1994, 14(1), 187-197.
193. Leski, M.L.; Valentine, S.L.; Coyle, J.T. L-type voltage-gated calcium channels modulate kainic acid neurotoxicity in cerebellar granule cells. Brain Res., 1999, 828(1-2), 27-40.
194. Obrenovitch, T.P.; Urenjak, J. Glutamate release inhibitors: a critical assessment of their action mechanism. Amino Acids, 1998, 14(1-3), 143-150.
195. Rothman, S.M.; Olney, J.W. Excitotoxicity and the NMDA receptor-still lethal after eight years. Trends Neurosci., 1995, 18(2), 57-58.
196. Zorumski, C.F.; Olney, J.W. Excitotoxic neuronal damage and neuropsychiatric disorders. Pharmacol. Ther., 1993, 59(2), 145-162.
197. Bialer, M. Chemical properties of antiepileptic drugs (AEDs). Adv. Drug Deliv. Rev., 2012, 64(10), 887-895.
198. DeLorenzo, R.J.; Sombati, S.; Coulter, D.A. Effects of topiramate on sustained repetitive firing and spontaneous recurrent seizure discharges in cultured hippocampal neurons. Epilepsia, 2000, 41 Suppl. 1, S40-44.
199. McLean, M.J.; Bukhari, A.A.; Wamil, A.W. Effects of topiramate on sodium-dependent action-potential firing by mouse spinal cord neurons in cell culture. Epilepsia, 2000, 41 Suppl 1, S21-24.
200. Zona, C.; Ciotti, M.T.; Avoli, M. Topiramate attenuates voltage-gated sodium currents in rat cerebellar granule cells. Neurosci. Lett., 1997, 231(3), 123-126.
201. Taverna, S.; Sancini, G.; Mantegazza, M.; Franceschetti, S.; Avanzini, G. Inhibition of transient and persistent Na+ current fractions by the new anticonvulsant topiramate. J. Pharmacol. Exp. Ther., 1999, 288(3), 960-968.
202. Zhang, X.; Velumian, A.A.; Jones, O.T.; Carlen, P.L. Modulation of high-voltage-activated calcium channels in dentate granule cells by topiramate. Epilepsia, 2000, 41 Suppl 1, S52-60.
203. Gibbs, J.W., 3rd; Sombati, S.; DeLorenzo, R.J.; Coulter, D.A. Cellular actions of topiramate: blockade of kainate-evoked inward currents in cultured hippocampal neurons. Epilepsia, 2000, 41 Suppl 1, S10-16.
204. Skradski, S.; White, H.S. Topiramate blocks kainate-evoked cobalt influx into cultured neurons. Epilepsia, 2000, 41 Suppl 1, S45-47.
205. Angehagen, M.; Ben-Menachem, E.; Ronnback, L.; Hansson, E. Topiramate protects against glutamate- and kainate-induced neurotoxicity in primary neuronal-astroglial cultures. Epilepsy Res., 2003, 54(1), 63-71.
206. Kaminski, R.M.; Banerjee, M.; Rogawski, M.A. Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology, 2004, 46(8), 1097-1104.
207. Muir, K.W. Glutamate-based therapeutic approaches: clinical trials with NMDA antagonists. Curr. Opin. Pharmacol., 2006, 6(1), 53-60.
208. Meldrum, B.S. Update on the mechanism of action of antiepileptic drugs. Epilepsia, 1996, 37 Suppl 6, S4-11.
209. Schroder, W.; Seifert, G.; Huttmann, K.; Hinterkeuser, S.; Steinhauser, C. AMPA receptor-mediated modulation of inward rectifier K+ channels in astrocytes of mouse hippocampus. Mol. Cell. Neurosci., 2002, 19(3), 447-458.
210. Qian, J.; Noebels, J.L. Topiramate alters excitatory synaptic transmission in mouse hippocampus. Epilepsy Res., 2003, 55(3), 225-233.
211. White, H.S.; Brown, S.D.; Woodhead, J.H.; Skeen, G.A.; Wolf, H.H. Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia, 2000, 41 Suppl 1, S17-20.
212. White, H.S.; Brown, S.D.; Woodhead, J.H.; Skeen, G.A.; Wolf, H.H. Topiramate enhances GABA-mediated chloride flux and GABA-evoked chloride currents in murine brain neurons and increases seizure threshold. Epilepsy Res., 1997, 28(3), 167-179.
213. Herrero, A.I.; Del Olmo, N.; Gonzalez-Escalada, J.R.; Solis, J.M. Two new actions of topiramate: inhibition of depolarizing GABA(A)-mediated responses and activation of a potassium conductance. Neuropharmacology, 2002, 42(2), 210-220.
214. De Simone, G.; Scozzafava, A.; Supuran, C.T. Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem. Biol. Drug Des., 2009, 74(3), 317-321.
215. Maragakis, N.J.; Jackson, M.; Ganel, R.; Rothstein, J.D. Topiramate protects against motor neuron degeneration in organotypic spinal cord cultures but not in G93A SOD1 transgenic mice. Neurosci. Lett., 2003, 338(2), 107-110.
216. Cudkowicz, M.E.; Shefner, J.M.; Schoenfeld, D.A.; Zhang, H.; Andreasson, K.I.; Rothstein, J.D.; Drachman, D.B. Trial of celecoxib in amyotrophic lateral sclerosis. Ann. Neurol., 2006, 60(1), 22-31.
217. Desport, J.C.; Preux, P.M.; Truong, T.C.; Vallat, J.M.; Sautereau, D.; Couratier, P. Nutritional status is a prognostic factor for survival in ALS patients. Neurology, 1999, 53(5), 1059-1063.
218. Nizzardo, M.; Nardini, M.; Ronchi, D.; Salani, S.; Donadoni, C.; Fortunato, F.; Colciago, G.; Falcone, M.; Simone, C.; Riboldi, G.; Govoni, A.; Bresolin, N.; Comi, G.P.; Corti, S. Beta-lactam antibiotic offers neuroprotection in a spinal muscular atrophy model by multiple mechanisms. Exp. Neurol., 2011, 229(2), 214-225.
219. Miller, B.R.; Dorner, J.L.; Shou, M.; Sari, Y.; Barton, S.J.; Sengelaub, D.R.; Kennedy, R.T.; Rebec, G.V. Up-regulation of GLT1 expression increases glutamate uptake and attenuates the Huntington's disease phenotype in the R6/2 mouse. Neuroscience, 2008, 153(1), 329-337.
220. Chu, K.; Lee, S.T.; Sinn, D.I.; Ko, S.Y.; Kim, E.H.; Kim, J.M.; Kim, S.J.; Park, D.K.; Jung, K.H.; Song, E.C.; Lee, S.K.; Kim, M.; Roh, J.K. Pharmacological Induction of Ischemic Tolerance by Glutamate Transporter-1 (EAAT2) Upregulation. Stroke, 2007, 38(1), 177-182.
221. Thone-Reineke, C.; Neumann, C.; Namsolleck, P.; Schmerbach, K.; Krikov, M.; Schefe, J.H.; Lucht, K.; Hortnagl, H.; Godes, M.; Muller, S.; Rumschussel, K.; Funke-Kaiser, H.; Villringer, A.; Steckelings, U.M.; Unger, T. The beta-lactam antibiotic, ceftriaxone, dramatically improves survival, increases glutamate uptake and induces neurotrophins in stroke. J. Hypertens, 2008, 26(12), 2426-2435.
222. Lipski, J.; Wan, CK.; Bai, J.Z.; Pi, R.; Li, D.; Donnelly, D. Neuroprotective potential of ceftriaxone in in vitro models of stroke. Neuroscience, 2007, 146(2), 617-629.
223. Melzer, N.; Meuth, S.G.; Torres-Salazar, D.; Bittner, S.; Zozulya, A.L.; Weidenfeller, C; Kotsiari, A.; Stangel, M.; Fahlke, C; Wiendl, H. A beta-lactam antibiotic dampens excitotoxic inflammatory CNS damage in a mouse model of multiple sclerosis. PLoS One, 2008, 3(9), e3149.
224. Radouane, A.; Pehourcq, F.; Tramu, G.; Creppy, E.E.; Bannwarth, B. Influence of lipophilicity on the diffusion of cephalosporins into the cerebrospinal fluid. Fundam. Clin. Pharmacol, 1996, 10(3), 309-313.
225. Kim, K.; Lee, S.G.; Kegelman, T.P.; Su, Z.Z.; Das, S.K.; Dash, R.; Dasgupta, S.; Barral, P.M.; Hedvat, M.; Diaz, P.; Reed, J.C.; Stebbins, J.L.; Pellecchia, M.; Sarkar, D.; Fisher, P.B. Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics. J. Cell. Physiol., 2011, 226(10), 2484-2493.
226. Jiang, J.; Amara, S.G. New views of glutamate transporter structure and function: advances and challenges. Neuropharmacology, 2011, 60(1), 172-181.
227. Tian, G.; Lai, L.; Guo, H.; Lin, Y.; Butchbach, M.E.; Chang, Y.; Lin, C.L. Translational control of glial glutamate transporter EAAT2 expression. J. Biol. Chem., 2007, 282(3), 1727-1737.
228. Dunkel, P.; Chai, C.L.; Sperlagh, B.; Huleatt, P.B.; Matyus, P. Clinical utility of neuroprotective agents in neurodegenerative diseases: current status of drug development for Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral sclerosis. Expert Opin. Investig. Drugs, 2012, 21(9), 1267-1308.
229. Glicksman, M.A. The preclinical discovery of amyotrophic lateral sclerosis drugs. Expert Opin. Drug Discov., 2011, 6(11), 1127-1138.
230. Vincent, A.M.; Backus, C; Taubman, A.A.; Feldman, E.L. Identification of candidate drugs for the treatment of ALS. Amyotroph. Lateral. Scler. Other Motor. Neuron Disord, 2005, 6(1), 29-36.
231. Tikka, T.; Usenius, T.; Tenhunen, M.; Keinanen, R.; Koistinaho, J. Tetracycline derivatives and ceftriaxone, a cephalosporin antibiotic, protect neurons against apoptosis induced by ionizing radiation. J. Neurochem., 2001, 78(6), 1409-1414.
232. Carreer, R.; Deby-Dupont, G.; Deby, C; Jadoul, L.; Mathy, M. Oxidant-scavenging activities of beta-lactam agents. Eur. J. Clin. Microbiol. Infect. Dis., 1998, 17(1), 43-46.
233. Ji, H.F.; Shen, L.; Zhang, H.Y. Beta-lactam antibiotics are multipotent agents to combat neurological diseases. Biochem. Biophys. Res. Commun., 2005, 333(3), 661-663.
234. Karin, M. Nuclear factor-kappaB in cancer development and progression. Nature, 2006, 441(7092), 431-436.
235. Massa, P.T.; Aleyasin, H.; Park, D.S.; Mao, X.; Barger, S.W. NFkappaB in neurons? The uncertainty principle in neurobiology. J. Neurochem., 2006, 97(3), 607-618.
236. Su, Z.Z.; Leszczyniecka, M.; Kang, D.C.; Sarkar, D.; Chao, W.; Volsky, D.J.; Fisher, P.B. Insights into glutamate transport regulation in human astrocytes: cloning of the promoter for excitatory amino acid transporter 2 (EAAT2). Proc. Natl. Acad. Sci. USA, 2003, 100(4), 1955-1960.
237. Sitcheran, R.; Gupta, P.; Fisher, P.B.; Baldwin, A.S. Positive and negative regulation of EAAT2 by NF-kappaB: a role for N-myc in TNFalpha-controlled repression. EMBO J., 2005, 24(3), 510-520.
238. Zelenaia, O.; Schlag, B.D.; Gochenauer, G.E.; Ganel, R.; Song, W.; Beesley, J.S.; Grinspan, J.B.; Rothstein, J.D.; Robinson, M.B. Epidermal growth factor receptor agonists increase expression of glutamate transporter GLT-1 in astrocytes through pathways dependent on phosphatidylinositol 3-kinase and transcription factor NF-kappaB. Mol. Pharmacol, 2000, 57(4), 667-678.
239. Lee, S.G.; Su, Z.Z.; Emdad, L.; Gupta, P.; Sarkar, D.; Borjabad, A.; Volsky, D.J.; Fisher, P.B. Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes. J. Biol. Chem., 2008, 283(19), 13116-13123.
240. Nau, R.; Prange, H.W.; Muth, P.; Mahr, G.; Menck, S.; Kolenda, H.; Sorgel, F. Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges. Antimicrob. Agents Chemother., 1993, 37(7), 1518-1524.
241. Berry, J.D.; Shefner, J.M.; Conwit, R.; Schoenfeld, D.; Keroack, M.; Felsenstein, D.; Krivickas, L.; David, W.S.; Vriesendorp, F.; Pestronk, A.; Caress, J.B.; Katz, J.; Simpson, E.; Rosenfeld, J.; Pascuzzi, R.; Glass, J.; Rezania, K.; Rothstein, J.D.; Greenblatt, D.J.; Cudkowicz, M.E. Design and initial results of a multi-phase randomized trial of ceftriaxone in amyotrophic lateral sclerosis. PLoS One, 2013, 8(4), e61177.
242. Chappell, A.S.; Sander, J.W.; Brodie, M.J.; Chadwick, D.; Lledo, A.; Zhang, D.; Bjerke, J.; Kiesler, G.M.; Arroyo, S. A crossover, add-on trial of talampanel in patients with refractory partial seizures. Neurology, 2002, 58(11), 1680-1682.
243. Langan, Y.M.; Lucas, R.; Jewell, H.; Toublanc, N.; Schaefer, H.; Sander, J.W.; Patsalos, P.N. Talampanel, a new antiepileptic drug: single- and multiple-dose pharmacokinetics and initial 1-week experience in patients with chronic intractable epilepsy. Epilepsia, 2003, 44(1), 46-53.
244. Czuczwar, S.J.; Swiader, M.; Kuzniar, H.; Gasior, M.; Kleinrok, Z. LY 300164, a novel antagonist of AMPA/kainate receptors, potentiates the anticonvulsive activity of antiepileptic drugs. Eur. J. Pharmacol., 1998, 359(2-3), 103-109.
245. Borowicz, K.K.; Kleinrok, Z.; Czuczwar, S.J. Glutamate receptor antagonists differentially affect the protective activity of conventional antiepileptics against amygdala-kindled seizures in rats. Eur. Neuropsychopharmacol., 2001, 11(1), 61-68.
246. Howes, J.F.; Bell, C. Talampanel. Neurotherapeutics, 2007, 4(1), 126-129.
247. Chimirri, A.; De Luca, L.; Ferro, S.; De Sarro, G.; Ciranna, L.; Gitto, R. Combined strategies for the discovery of ionotropic glutamate receptor antagonists. ChemMedChem, 2009, 4(6), 917-922.
248. Gitto, R.; Damiano, F.M.; Mader, P.; De Luca, L.; Ferro, S.; Supuran, C.T.; Vullo, D.; Brynda, J.; Rezacova, P.; Chimirri, A. Synthesis, structure-activity relationship studies, and X-ray crystallographic analysis of arylsulfonamides as potent carbonic anhydrase inhibitors. J. Med. Chem., 2012, 55(8), 3891-3899.
249. Russo, E.; Gitto, R.; Citraro, R.; Chimirri, A.; De Sarro, G. New AMPA antagonists in epilepsy. Expert Opin. Investig. Drugs, 2012, 21(9), 1371-1389.
250. Chimirri, A.; De Sarro, G.; De Sarro, A.; Gitto, R.; Quartarone, S.; Zappala, M.; Constanti, A.; Libri, V. 3,5-Dihydro-4H-2,3-benzodiazepine-4-thiones: a new class of AMPA receptor antagonists. J. Med. Chem., 1998, 41(18), 3409-3416.
251. Chimirri, A.; De Sarro, G.; De Sarro, A.; Gitto, R.; Grasso, S.; Quartarone, S.; Zappala, M.; Giusti, P.; Libri, V.; Constanti, A.; Chapman, A.G. 1-Aryl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones: novel AMPA receptor antagonists. J. Med. Chem., 1997, 40(8), 1258-1269.
252. Ritz, M.; Wang, C.; Micale, N.; Ettari, R.; Niu, L. Mechanism of Inhibition of the GluA2 AMPA Receptor Channel Opening: the Role of 4-Methyl versus 4-Carbonyl Group on the Diazepine Ring of 2,3-Benzodiazepine Derivatives. ACS Chem. Neurosci., 2011, 2(9), 506-513.
253. Qneibi, M.S.; Micale, N.; Grasso, S.; Niu, L. Mechanism of inhibition of GluA2 AMPA receptor channel opening by 2,3-benzodiazepine derivatives: functional consequences of replacing a 7,8-methylenedioxy with a 7,8-ethylenedioxy moiety. Biochemistry, 2012, 51(8), 1787-1795.
254. Macchiarulo, A.; De Luca, L.; Costantino, G.; Barreca, M.L.; Gitto, R.; Pellicciari, R.; Chimirri, A. QSAR study of anticonvulsant negative allosteric modulators of the AMPA receptor. J. Med. Chem., 2004, 47(7), 1860-1863.
255. Wang, C.; Niu, L. Mechanism of inhibition of the GluA2 AMPA receptor channel opening by talampanel and its enantiomer: the stereochemistry of the 4-methyl group on the diazepine ring of 2,3-benzodiazepine derivatives. ACS Chem. Neurosci., 2013, 4(4), 635-644.
256. Barreca, M.L.; Gitto, R.; Quartarone, S.; De Luca, L.; De Sarro, G.; Chimirri, A. Pharmacophore modeling as an efficient tool in the discovery of novel noncompetitive AMPA receptor antagonists. J. Chem. Inf. Comput. Sci., 2003, 43(2), 651-655.
257. Rezessy, B.; Solyom, S. Advanced Pharmacophore Model of Non-Competitive AMPA Antagonist 2,3-benzodiazepines. Lett. Drug Des. Disc., 2004, 1(3), 217-223.
258. Cotton, J.L.; Partin, K.M. The contributions of GluR2 to allosteric modulation of AMPA receptors. Neuropharmacology, 2000, 39(1), 21-31.
259. Elger, B.; Schneider, M.; Winter, E.; Carvelli, L.; Bonomi, M.; Fracasso, C.; Guiso, G.; Colovic, M.; Caccia, S.; Mennini, T. Optimized synthesis of AMPA receptor antagonist ZK 187638 and neurobehavioral activity in a mouse model of neuronal ceroid lipofuscinosis. ChemMedChem, 2006, 1(10), 1142-1148.
260. Tortarolo, M.; Grignaschi, G.; Calvaresi, N.; Zennaro, E.; Spaltro, G.; Colovic, M.; Fracasso, C.; Guiso, G.; Elger, B.; Schneider, H.; Seilheimer, B.; Caccia, S.; Bendotti, C. Glutamate AMPA receptors change in motor neurons of SOD1G93A transgenic mice and their inhibition by a noncompetitive antagonist ameliorates the progression of amytrophic lateral sclerosis-like disease. J. Neurosci. Res., 2006, 83(1), 134-146.
261. Zaccara, G.; Giovannelli, F.; Cincotta, M.; Iudice, A. AMPA receptor inhibitors for the treatment of epilepsy: the role of perampanel. Expert Rev. Neurother., 2013, 13(6), 647-655.
262. Hsu, W.W.; Sing, C.W.; He, Y.; Worsley, A.J.; Wong, I.C.; Chan, E.W. Systematic review and meta-analysis of the efficacy and safety of perampanel in the treatment of partial-onset epilepsy. CNS Drugs, 2013, 27(10), 817-827.
263. Bialer, M.; White, H.S. Key factors in the discovery and development of new antiepileptic drugs. Nat. Rev. Drug Discov., 2010, 9(1), 68-82.
264. Gitto, R.; Orlando, V.; Quartarone, S.; De Sarro, G.; De Sarro, A.; Russo, E.; Ferreri, G.; Chimirri, A. Synthesis and evaluation of pharmacological properties of novel annelated 2,3-benzodiazepine derivatives. J. Med. Chem., 2003, 46(17), 3758-3761.
265. Gitto, R.; Barreca, M.L.; De Luca, L.; De Sarro, G.; Ferreri, G.; Quartarone, S.; Russo, E.; Constanti, A.; Chimirri, A. Discovery of a novel and highly potent noncompetitive AMPA receptor antagonist. J. Med. Chem., 2003, 46(1), 197-200.
266. Sobolevsky, A.I.; Rosconi, M.P.; Gouaux, E. X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor. Nature, 2009, 462(7274), 745-756.
267. Hogner, A.; Greenwood, J.R.; Liljefors, T.; Lunn, M.L.; Egebjerg, J.; Larsen, I.K.; Gouaux, E.; Kastrup, J.S. Competitive antagonism of AMPA receptors by ligands of different classes: crystal structure of ATPO bound to the GluR2 ligand-binding core, in comparison with DNQX. J. Med. Chem., 2003, 46(2), 214-221.
268. Menuz, K.; Stroud, R.M.; Nicoll, R.A.; Hays, F.A. TARP auxiliary subunits switch AMPA receptor antagonists into partial agonists. Science, 2007, 318(5851), 815-817.
269. Armstrong, N.; Gouaux, E. Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core. Neuron, 2000, 28(1), 165-181.
270. Kaczor, A.A.; Kijkowska-Murak, U.A.; Kronbach, C.; Unverferth, K.; Matosiuk, D. Modeling of glutamate GluR6 receptor and its interactions with novel noncompetitive antagonists. J. Chem. Inf. Model., 2009, 49(4), 1094-1104.
271. Kaczor, A.A.; Kijkowska-Murak, U.A.; Matosiuk, D. Theoretical studies on the structure and symmetry of the transmembrane region of glutamatergic GluR5 receptor. J. Med. Chem., 2008, 51(13), 3765-3776.
272. Van Damme, P.; Van Den Bosch, L.; Van Houtte, E.; Callewaert, G.; Robberecht, W. GluR2-dependent properties of AMPA receptors determine the selective vulnerability of motor neurons to excitotoxicity. J. Neurophysiol., 2002, 88(3), 1279-1287.
273. Vandenberghe, W.; Robberecht, W.; Brorson, J.R. AMPA receptor calcium permeability, GluR2 expression, and selective motoneuron vulnerability. J. Neurosci., 2000, 20(1), 123-132.
274. Van Den Bosch, L.; Vandenberghe, W.; Klaassen, H.; Van Houtte, E.; Robberecht, W. Ca(2+)-permeable AMPA receptors and selective vulnerability of motor neurons. J. Neurol. Sci., 2000, 180(1-2), 29-34.
275. De Sarro, G.; Gitto, R.; Russo, E.; Ibbadu, G.F.; Barreca, M.L.; De Luca, L.; Chimirri, A. AMPA receptor antagonists as potential anticonvulsant drugs. Curr. Top. Med. Chem., 2005, 5(1), 31-42.
276. Solyom, S. Research on new AMPA antagonists of 2,3-benzodiazepine type. Pharmazie, 2001, 56 Suppl 1, S62-66.
277. Denes, L.; Szilagyi, G.; Gal, A.; Nagy, Z. Talampanel a non-competitive AMPA-antagonist attenuates caspase-3 dependent apoptosis in mouse brain after transient focal cerebral ischemia. Brain Res. Bull., 2006, 70(3), 260-262.
278. Canton, T.; Bohme, G.A.; Boireau, A.; Bordier, F.; Mignani, S.; Jimonet, P.; Jahn, G.; Alavijeh, M.; Stygall, J.; Roberts, S.; Brealey, C.; Vuilhorgne, M.; Debono, M.W.; Le Guern, S.; Laville, M.; Briet, D.; Roux, M.; Stutzmann, J.M.; Pratt, J. RPR 119990, a novel alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist: synthesis, pharmacological properties, and activity in an animal model of amyotrophic lateral sclerosis. J. Pharmacol. Exp. Ther., 2001, 299(1), 314-322.
279. Van Damme, P.; Leyssen, M.; Callewaert, G.; Robberecht, W.; Van Den Bosch, L. The AMPA receptor antagonist NBQX prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis. Neurosci. Lett., 2003, 343(2), 81-84.
280. Pascuzzi, R.M.; Shefner, J.; Chappell, A.S.; Bjerke, J.S.; Tamura, R.; Chaudhry, V.; Clawson, L.; Haas, L.; Rothstein, J.D. A phase II trial of talampanel in subjects with amyotrophic lateral sclerosis. Amyotroph. Lateral. Scler., 2010, 11(3), 266-271.
281. Gerzon, K.; Krumkalns, E.V.; Brindle, R.L.; Marshall, F.J.; Root, M.A. The Adamantyl Group in Medicinal Agents. I. Hypoglycemic N-Arylsulfonyl-N'-Adamantylureas. J. Med. Chem., 1963, 6, 760-763.
282. Parsons, C.G.; Danysz, W.; Quack, G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist - a review of preclinical data. Neuropharmacology, 1999, 38(6), 735-767.
283. Bormann, J. Memantine is a potent blocker of N-methyl-D-aspartate (NMDA) receptor channels. Eur. J. Pharmacol., 1989, 166(3), 591-592.
284. Kornhuber, J.; Bormann, J.; Retz, W.; Hubers, M.; Riederer, P. Memantine displaces [3H]MK-801 at therapeutic concentrations in postmortem human frontal cortex. Eur. J. Pharmacol., 1989, 166(3), 589-590.
285. Kornhuber, J.; Bormann, J.; Hubers, M.; Rusche, K.; Riederer, P. Effects of the 1-amino-adamantanes at the MK-801-binding site of the NMDA-receptor-gated ion channel: a human postmortem brain study. Eur. J. Pharmacol., 1991, 206(4), 297-300.
286. Parsons, C.G.; Gruner, R.; Rozental, J.; Millar, J.; Lodge, D. Patch clamp studies on the kinetics and selectivity of N-methyl-D-aspartate receptor antagonism by memantine (1-amino-3,5-dimethyladamantan). Neuropharmacology, 1993, 32(12), 1337-1350.
287. Parsons, C.G.; Quack, G.; Bresink, I.; Baran, L.; Przegalinski, E.; Kostowski, W.; Krzascik, P.; Hartmann, S.; Danysz, W. Comparison of the potency, kinetics and voltage-dependency of a series of uncompetitive NMDA receptor antagonists in vitro with anticonvulsive and motor impairment activity in vivo. Neuropharmacology, 1995, 34(10), 1239-1258.
288. Jain, K.K. Evaluation of memantine for neuroprotection in dementia. Expert Opin. Investig. Drugs, 2000, 9(6), 1397-1406.
289. Sonkusare, S.K.; Kaul, C.L.; Ramarao, P. Dementia of Alzheimer's disease and other neurodegenerative disorders-memantine, a new hope. Pharmacol. Res., 2005, 51(1), 1-17.
290. Schmitt, H.P. On the paradox of ion channel blockade and its benefits in the treatment of Alzheimer disease. Med. Hypotheses, 2005, 65(2), 259-265.
291. Lipton, S.A. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat. Rev. Drug Discov., 2006, 5(2), 160-170.
292. Parsons, C.G.; Stoffler, A.; Danysz, W. Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system-too little activation is bad, too much is even worse. Neuropharmacology, 2007, 53(6), 699-723.
293. Zdanys, K.; Tampi, R.R. A systematic review of off-label uses of memantine for psychiatric disorders. Prog. Neuropsycho pharmacol. Biol. Psychiatry, 2008, 32(6), 1362-1374.
294. Kornhuber, J.; Quack, G. Cerebrospinal fluid and serum concentrations of the N-methyl-D-aspartate (NMDA) receptor antagonist memantine in man. Neurosci. Lett., 1995, 195(2), 137-139.
295. Johnson, J.W.; Kotermanski, S.E. Mechanism of action of memantine. Curr. Opin. Pharmacol., 2006, 6(1), 61-67.
296. Long, S.B.; Tao, X.; Campbell, E.B.; MacKinnon, R. Atomic structure of a voltage-dependent K+ channel in a lipid membranelike environment. Nature, 2007, 450(7168), 376-382.
297. Kashiwagi, K.; Masuko, T.; Nguyen, C.D.; Kuno, T.; Tanaka, I.; Igarashi, K.; Williams, K. Channel blockers acting at N-methyl-D-aspartate receptors: differential effects of mutations in the vestibule and ion channel pore. Mol. Pharmacol., 2002, 61(3), 533-545.
298. Limapichat, W.; Yu, W.Y.; Branigan, E.; Lester, H.A.; Dougherty, D.A. Key binding interactions for memantine in the NMDA receptor. ACS Chem. Neurosci., 2013, 4(2), 255-260.
299. Jirgensons, A.; Kauss, V.; Kalvinsh, I.; Gold, M.R.; Danysz, W.; Parsons, C.G.; Quack, G. Synthesis and structure-affinity relationships of 1,3, 5-alkylsubstituted cyclohexylamines binding at NMDA receptor PCP site. Eur. J. Med. Chem., 2000, 35(6), 555-565.
300. Wong, E.H.; Kemp, J.A.; Priestley, T.; Knight, A.R.; Woodruff, G.N.; Iversen, L.L. The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc. Natl. Acad. Sci. USA, 1986, 83(18), 7104-7108.
301. Huettner, J.E.; Baughman, R.W. The pharmacology of synapses formed by identified corticocollicular neurons in primary cultures of rat visual cortex. J. Neurosci., 1988, 8(1), 160-175.
302. Fultz, T.J.; Wang, Y. Therapeutic conjugates and methods of using same, WO2007065036 A3, 2007.
303. Furukawa, H.; Singh, S.K.; Mancusso, R.; Gouaux, E. Subunit arrangement and function in NMDA receptors. Nature, 2005, 438(7065), 185-192.
304. Rogawski, M.A.; Wenk, G.L. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev., 2003, 9(3), 275-308.
305. Parsons, C.G.; Gilling, K. Memantine as an example of a fast, voltage-dependent, open channel N-methyl-D-aspartate receptor blocker. Methods Mol. Biol., 2007, 403, 15-36.
306. Robinson, K.M.; Lacey, S.C.; Grugan, P.; Glosser, G.; Grossman, M.; McCluskey, L.F. Cognitive functioning in sporadic amyotrophic lateral sclerosis: a six month longitudinal study. J. Neurol. Neurosurg. Psychiatry, 2006, 77(5), 668-670.
307. McKay, S.; Bengtson, C.P.; Bading, H.; Wyllie, D.J.; Hardingham, G.E. Recovery of NMDA receptor currents from MK-801 blockade is accelerated by Mg2+ and memantine under conditions of agonist exposure. Neuropharmacology, 2013, 74, 119-125.
308. Chen, H.S.; Lipton, S.A. Pharmacological implications of two distinct mechanisms of interaction of memantine with N-methyl-D-aspartate-gated channels. J. Pharmacol. Exp. Ther., 2005, 314(3), 961-971.
309. Sobolevsky, A.I.; Koshelev, S.G.; Khodorov, B.I. Interaction of memantine and amantadine with agonist-unbound NMDA-receptor channels in acutely isolated rat hippocampal neurons. J. Physiol., 1998, 512 ( Pt 1), 47-60.
310. Kotermanski, S.E.; Wood, J.T.; Johnson, J.W. Memantine binding to a superficial site on NMDA receptors contributes to partial trapping. J. Physiol., 2009, 587(Pt 19), 4589-4604.
311. Robinson, D.M.; Keating, G.M. Memantine: a review of its use in Alzheimer's disease. Drugs, 2006, 66(11), 1515-1534.
312. Tomek, S.E.; Lacrosse, A.L.; Nemirovsky, N.E.; Olive, M.F. NMDA Receptor Modulators in the Treatment of Drug Addiction. Pharmaceuticals (Basel.), 2013, 6(2), 251-268.
313. Chen, H.S.; Lipton, S.A. The chemical biology of clinically tolerated NMDA receptor antagonists. J. Neurochem., 2006, 97(6), 1611-1626.
314. Chen, H.S.; Pellegrini, J.W.; Aggarwal, S.K.; Lei, S.Z.; Warach, S.; Jensen, F.E.; Lipton, S.A. Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity. J. Neurosci., 1992, 12(11), 4427-4436.
315. Kotermanski, S.E.; Johnson, J.W. Mg2+ imparts NMDA receptor subtype selectivity to the Alzheimer's drug memantine. J. Neurosci., 2009, 29(9), 2774-2779.
316. Olive, M.F.; Cleva, R.M.; Kalivas, P.W.; Malcolm, R.J. Glutamatergic medications for the treatment of drug and behavioral addictions. Pharmacol. Biochem. Behav., 2012, 100(4), 801-810.
317. ∗ nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal neurons. J. Pharmacol. Exp. Ther., 2005, 312(3), 1195-1205.
318. Snyder, E.M.; Nong, Y.; Almeida, C.G.; Paul, S.; Moran, T.; Choi, E.Y.; Nairn, A.C.; Salter, M.W.; Lombroso, P.J.; Gouras, G.K.; Greengard, P. Regulation of NMDA receptor trafficking by amyloid-beta. Nat. Neurosci., 2005, 8(8), 1051-1058.
319. Li, L.; Sengupta, A.; Haque, N.; Grundke-Iqbal, I.; Iqbal, K. Memantine inhibits and reverses the Alzheimer type abnormal hyperphosphorylation of tau and associated neurodegeneration. FEBS Lett., 2004, 566(1-3), 261-269.
320. Murayama, S.; Mori, H.; Ihara, Y.; Bouldin, T.W.; Suzuki, K.; Tomonaga, M. Immunocytochemical and ultrastructural studies of lower motor neurons in amyotrophic lateral sclerosis. Ann. Neurol., 1990, 27(2), 137-148.
321. Brettschneider, J.; Petzold, A.; Sussmuth, S.D.; Ludolph, A.C.; Tumani, H. Axonal damage markers in cerebrospinal fluid are increased in ALS. Neurology, 2006, 66(6), 852-856.
322. Jimenez-Jimenez, F.J.; Hernanz, A.; Medina-Acebron, S.; de Bustos, F.; Zurdo, J.M.; Alonso, H.; Puertas, I.; Barcenilla, B.; Sayed, Y.; Cabrera-Valdivia, F. Tau protein concentrations in cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Acta Neurol. Scand., 2005, 111(2), 114-117.
323. Levine, T.D.; Bowser, R.; Hank, N.; Saperstein, D. A pilot trial of memantine and riluzole in ALS: correlation to CSF biomarkers. Amyotroph. Lateral. Scler., 2010, 11(6), 514-519.
324. Osborne, N.N.; Quack, G. Memantine stimulates inositol phosphates production in neurones and nullifies N-methyl-D-aspartate-induced destruction of retinal neurones. Neurochem. Int., 1992, 21(3), 329-336.
325. Lampe, H.; Bigalke, H. Modulation of glycine-activated membrane current by adamantane derivatives. Neuroreport, 1991, 2(7), 373-376.
326. Wenk, G.L.; Zajaczkowski, W.; Danysz, W. Neuroprotection of acetylcholinergic basal forebrain neurons by memantine and neurokinin B. Behav. Brain Res., 1997, 83(1-2), 129-133.
327. Miguel-Hidalgo, J.J.; Alvarez, X.A.; Cacabelos, R.; Quack, G. Neuroprotection by memantine against neurodegeneration induced by beta-amyloid(1-40). Brain Res., 2002, 958(1), 210-221.
328. Wang, R.; Zhang, D. Memantine prolongs survival in an amyotrophic lateral sclerosis mouse model. Eur. J. Neurosci., 2005, 22(9), 2376-2380.
329. Joo, I.S.; Hwang, D.H.; Seok, J.I.; Shin, S.K.; Kim, S.U. Oral administration of memantine prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis. J. Clin. Neurol., 2007, 3(4), 181-186.
330. de Carvalho, M.; Pinto, S.; Costa, J.; Evangelista, T.; Ohana, B.; Pinto, A. A randomized, placebo-controlled trial of memantine for functional disability in amyotrophic lateral sclerosis. Amyotroph. Lateral. Scler., 2010, 11(5), 456-460.
331. Reid, J.G.; Gitlin, M.J.; Altshuler, L.L. Lamotrigine in psychiatric disorders. J. Clin. Psychiatry, 2013, 74(7), 675-684.
332. Vajda, F.J.; Dodd, S.; Horgan, D. Lamotrigine in epilepsy, pregnancy and psychiatry - a drug for all seasons? J. Clin. Neurosci., 2013, 20(1), 13-16.
333. Leach, M.J.; Marden, C.M.; Miller, A.A. Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanism of action. Epilepsia, 1986, 27(5), 490-497.
334. Knowles, S.R.; Shapiro, L.E.; Shear, N.H. Anticonvulsant hypersensitivity syndrome: incidence, prevention and management. Drug Saf., 1999, 21(6), 489-501.
335. Wang, X.Q.; Shi, X.B.; Au, R.; Chen, F.S.; Wang, F.; Lang, S.Y. Influence of chemical structure on skin reactions induced by antiepileptic drugs-The role of the aromatic ring. Epilepsy Res., 2011, 94(3), 213-217.
336. Kuo, C.C. A common anticonvulsant binding site for phenytoin, carbamazepine, and lamotrigine in neuronal Na+ channels. Mol. Pharmacol., 1998, 54(4), 712-721.
337. Ma, X.; Poon, T.Y.; Wong, P.T.; Chui, W.K. Synthesis and in vitro evaluation of 2,4-diamino-1,3,5-triazine derivatives as neuronal voltage-gated sodium channel blockers. Bioorg. Med. Chem. Lett., 2009, 19(19), 5644-5647.
338. Kaushik, D.; Khan, S.A.; Chawla, G.; Kumar, S. N'-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene] 2/4-substituted hyd-razides: synthesis and anticonvulsant activity. Eur. J. Med. Chem., 2010, 45(9), 3943-3949.
339. Ding, H.G.; Wang, B.E.; Zhao, C.H.; Jia, J.D.; Xu, Y.L.; Tang, S.Z. Effects on intracellular Ca2+ and expression of L-type voltage-operated calcium channel protein in activated hepatic stellate cells stimulated by Chinese herbal compound 861. Zhonghua Gan Zang Bing Za Zhi, 2005, 13(12), 922-926.
340. Cronin, N.B.; O'Reilly, A.; Duclohier, H.; Wallace, B.A. Binding of the anticonvulsant drug lamotrigine and the neurotoxin batrachotoxin to voltage-gated sodium channels induces conformational changes associated with block and steady-state activation. J. Biol. Chem., 2003, 278(12), 10675-10682.
341. Yarov-Yarovoy, V.; Brown, J.; Sharp, E.M.; Clare, J.J.; Scheuer, T.; Catterall, W.A. Molecular determinants of voltage-dependent gating and binding of pore-blocking drugs in transmembrane segment IIIS6 of the Na(+) channel alpha subunit. J. Biol. Chem., 2001, 276(1), 20-27.
342. Xie, X.; Dale, T.J.; John, V.H.; Cater, H.L.; Peakman, T.C.; Clare, J.J. Electrophysiological and pharmacological properties of the human brain type IIA Na+ channel expressed in a stable mammalian cell line. Pflugers Arch., 2001, 441(4), 425-433.
343. Reynolds, E.H., Anticonvulsants, folic acid, and epilepsy. Lancet, 1973, 1(7816), 1376-1378.
344. Lingamaneni, R.; Hemmings, H.C., Jr. Effects of anticonvulsants on veratridine- and KCl-evoked glutamate release from rat cortical synaptosomes. Neurosci. Lett., 1999, 276(2), 127-130.
345. Fitton, A.; Goa, K.L. Lamotrigine. An update of its pharmacology and therapeutic use in epilepsy. Drugs, 1995, 50(4), 691-713.
346. Wang, S.J.; Sihra, T.S.; Gean, P.W. Lamotrigine inhibition of glutamate release from isolated cerebrocortical nerve terminals (synaptosomes) by suppression of voltage-activated calcium channel activity. Neuroreport, 2001, 12(10), 2255-2258.
347. Sitges, M.; Guarneros, A.; Nekrassov, V. Effects of carbamazepine, phenytoin, valproic acid, oxcarbazepine, lamotrigine, topiramate and vinpocetine on the presynaptic Ca2+ channel-mediated release of [3H]glutamate: comparison with the Na+ channel-mediated release. Neuropharmacology, 2007, 53(7), 854-862.
348. Sitges, M.; Chiu, L.M.; Guarneros, A.; Nekrassov, V. Effects of carbamazepine, phenytoin, lamotrigine, oxcarbazepine, topiramate and vinpocetine on Na+ channel-mediated release of [3H]glutamate in hippocampal nerve endings. Neuropharmacology, 2007, 52(2), 598-605.
349. Li, X.; Ketter, T.A.; Frye, M.A. Synaptic, intracellular, and neuroprotective mechanisms of anticonvulsants: are they relevant for the treatment and course of bipolar disorders? J. Affect. Disord., 2002, 69(1-3), 1-14.
350. Stefani, A.; Spadoni, F.; Bernardi, G. Differential inhibition by riluzole, lamotrigine, and phenytoin of sodium and calcium currents in cortical neurons: implications for neuroprotective strategies. Exp. Neurol., 1997, 147(1), 115-122.
351. Phillips, I.; Martin, K.F.; Thompson, K.S.; Heal, D.J. Weak blockade of AMPA receptor-mediated depolarisations in the rat cortical wedge by phenytoin but not lamotrigine or carbamazepine. Eur. J. Pharmacol., 1997, 337(2-3), 189-195.
352. Lee, C.Y.; Fu, W.M.; Chen, C.C.; Su, M.J.; Liou, H.H. Lamotrigine inhibits postsynaptic AMPA receptor and glutamate release in the dentate gyrus. Epilepsia, 2008, 49(5), 888-897.
353. Casanovas, A.; Ribera, J.; Hukkanen, M.; Riveros-Moreno, V.; Esquerda, J.E. Prevention by lamotrigine, MK-801 and N omega-nitro-L-arginine methyl ester of motoneuron cell death after neonatal axotomy. Neuroscience, 1996, 71(2), 313-325.
354. Ryberg, H.; Askmark, H.; Persson, L.I. A double-blind randomized clinical trial in amyotrophic lateral sclerosis using lamotrigine: effects on CSF glutamate, aspartate, branched-chain amino acid levels and clinical parameters. Acta Neurol. Scand., 2003, 108(1), 1-8.
355. Eriksson, A.S.; O'Connor, W.T. Analysis of CSF amino acids in young patients with generalised refractory epilepsy during an addon study with lamotrigine. Epilepsy Res., 1999, 34(1), 75-83.
356. Lunn, J.S.; Sakowski, S.A.; Feldman, E.L. Stem cell therapies for amyotrophic lateral sclerosis: Recent advances and prospects for the future. Stem Cells, 2014, 32(5), 1099-1109.
357. Navarro-Yepes, J.; Zavala-Flores, L.; Anandhan, A.; Wang, F.; Skotak, M.; Chandra, N.; Li, M.; Pappa, A.; Martinez-Fong, D.; Del Razo, L.M.; Quintanilla-Vega, B.; Franco, R. Antioxidant gene therapy against neuronal cell death. Pharmacol. Ther., 2013, 142(2), 206-230.
358. Geldenhuys, W.J.; Van der Schyf, C.J. Designing drugs with multitarget activity: the next step in the treatment of neurodegenerative disorders. Expert Opin. Drug Discov., 2013, 8(2), 115-129.
359. Otto, M.; Bowser, R.; Turner, M.; Berry, J.; Brettschneider, J.; Connor, J.; Costa, J.; Cudkowicz, M.; Glass, J.; Jahn, O.; Lehnert, S.; Malaspina, A.; Parnetti, L.; Petzold, A.; Shaw, P.; Sherman, A.; Steinacker, P.; Sussmuth, S.; Teunissen, C.; Tumani, H.; Wuolikainen, A.; Ludolph, A. Roadmap and standard operating procedures for biobanking and discovery of neurochemical markers in ALS. Amyotroph. Lateral. Scler., 2012, 13(1), 1-10.
360. Trushina, E.; Mielke, M.M. Recent advances in the application of metabolomics to Alzheimer's Disease. Biochim. Biophys. Acta, 2014, 1842(8), 1232-1239.