Neuronal potassium channel openers in the management of epilepsy: Role and potential of retigabine

Clinical Pharmacology: Advances and Applications

Volumn 2, Issue 1, 2010, Pages 225-236

  Barrese, Vincenzo ^a   Miceli, Francesco ^b   Soldovieri, Maria Virginia ^c   Ambrosino, Paolo ^c   Iannotti, Fabio Arturo ^c   Cilio, Maria Roberta ^b   Taglialatela, Maurizio ^a,c  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

^c UNIVERSITY OF MOLISE   (Italy)

Author keywords

Antiepileptic drugs; Epilepsy; Kv7 channels; Potassium channels; Retigabine

Indexed keywords

FLUPIRTINE; PLACEBO; RETIGABINE; UNCLASSIFIED DRUG; VALPROIC ACID; VOLTAGE GATED POTASSIUM CHANNEL; VOLTAGE GATED POTASSIUM CHANNEL KV7;

ADD ON THERAPY; ANTICONVULSANT ACTIVITY; ASTHENIA; CLINICAL TRIAL; CONFUSION; CONVULSION; COORDINATION DISORDER; DISTRIBUTION VOLUME; DIZZINESS; DOSE RESPONSE; DRUG ABSORPTION; DRUG BINDING SITE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; EPILEPSY; FOCAL EPILEPSY; GAIT DISORDER; HEADACHE; HUMAN; HYPERKINESIA; HYPOKINESIA; KIDNEY DISEASE; NERVE EXCITABILITY; NONHUMAN; PATHOPHYSIOLOGY; PATIENT CARE; PLASMA CONCENTRATION-TIME CURVE; PROTEIN FUNCTION; QT PROLONGATION; REVIEW; SEIZURE; SEX DIFFERENCE; SOMNOLENCE; TREMOR; URINARY TRACT DISEASE;

EID: 78650722317     PISSN: None     EISSN: 11791438     Source Type: Journal    
DOI: 10.2147/CPAA.S15369     Document Type: Review

References (93)

1. Noebels JL. Targeting epilepsy genes. Neuron. 1996;16(2):241-244.
2. Plosker GL, Scott LJ. Retigabine: In partial seizures. CNS Drugs. 2006;20(7):601-608.
3. Forsgren L, Beghi E, Oun A, Sillanpää M. The epidemiology of epilepsy in Europe - a systematic review. Eur J Neurol. 2005;12(4):245-253.
4. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010;51(4):676-685.
5. Shieh CC, Coghlan M, Sullivan JP, Gopalakrishnan M. Potassium channels: Molecular defects, diseases, and therapeutic opportunities. Pharmacol Rev. 2000;52(4):557-594.
6. + current in a vertebrate neurone. Nature. 1980;283(5748): 673-676.
7. Halliwell JV, Adams PR. Voltage-clamp analysis of muscarinic excita- tion in hippocampal neurons. Brain Res. 1982;250(1):71-92.
8. + channels and the molecular pathogenesis of epilepsy: Implications for therapy. Trends Neurosci. 2000;23(9):393-398.
9. + channels expressed in HEK293T cells. Eur J Pharmacol. 2003;462(1-3):25-32.
10. Marrion NV. Control of M-current. Annu Rev Physiol. 1997;59: 483-504.
11. Delmas P, Brown DA. Pathways modulating neural KCNQ/M (Kv7) potassium channels. Nat Rev Neurosci. 2005;6(11):850-862.
12. Singh NA, Charlier C, Stauffer D, et al. A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. Nat Genet. 1998;18(1):25-29.
13. Biervert C, Schroeder BC, Kubisch C, et al. A potassium channel muta- tion in neonatal human epilepsy. Science. 1998;279(5349):403-406.
14. Charlier C, Singh NA, Ryan SG, et al. A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nat Genet. 1998;18(1):53-55.
15. Wang Q, Curran ME, Splawski I, et al. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 1996;12(1):17-23.
16. Kubisch C, Schroeder BC, Friedrich T, et al. KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell. 1999;96(3):437-446.
17. + channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway. Proc Natl Acad Sci U S A. 2000; 97(8):4333-4338.
18. Iannotti FA, Panza E, Barrese V, Viggiano D, Soldovieri MV, Taglialatela M. Expression, localization, and pharmacological role of Kv7 potassium channels in skeletal muscle proliferation, differen- tiation, and survival after myotoxic insults. J Pharmacol Exp Ther. 2010;332(3):811-820.
19. Greenwood IA, Ohya S. New tricks for old dogs: KCNQ expression and role in smooth muscle. Br J Pharmacol. 2009;156(8): 1196-1203.
20. Lerche C, Scherer CR, Seebohm G, et al. Molecular cloning and functional expression of KCNQ5, a potassium channel subunit that may contribute to neuronal M-current diversity. J Biol Chem. 2000;275(29):22395-22400.
21. Brown DA, Passmore GM. Neural KCNQ (Kv7) channels. Br J Pharmacol. 2009;156(8):1185-1195.
22. Cooper EC, Aldape KD, Abosch A, et al. Colocalization and coas- sembly of two human brain M-type potassium channel subunits that are mutated in epilepsy. Proc Natl Acad Sci U S A. 2000;97(9): 4914-4919.
23. Wang HS, Pan S, Shi W, et al. KCNQ2 and KCNQ3 potassium channel subunits: Molecular correlates of the M-channel. Science. 1998;282(5395):1890-1893.
24. Bellini G, Miceli F, Soldovieri MV, Miraglia del Giudice E, Pascotto A, Taglialatela M. Benign familial neonatal seizures. In: Pagon RA, Bird TC, Dolan CR, Stephens K, editors. Gene Reviews [Internet]. Seattle, WA: University of Washington; 1993-2010.
25. Watanabe H, Nagata E, Kosakai A, et al. Disruption of the epilepsy KCNQ2 gene results in neural hyperexcitability. J Neurochem. 2000; 75(1):28-33.
26. Peters HC, Hu H, Pongs O, Storm JF, Isbrandt D. Conditional transgenic suppression of M channels in mouse brain reveals functions in neuronal excitability, resonance and behavior. Nat Neurosci. 2005;8(1): 51-60.
27. Yang Y, Beyer BJ, Otto JF, et al. Spontaneous deletion of epilepsy gene orthologs in a mutant mouse with a low electroconvulsive threshold. Hum Mol Genet. 2003;12(9):975-984.
28. Singh NA, Otto JF, Dahle EJ, et al. Mouse models of human KCNQ2 and KCNQ3 mutations for benign familial neonatal convulsions show seizures and neuronal plasticity without synaptic reorganization. J Physiol. 2008;586(14):3405-3423.
29. Boscia F, Annunziato L, Taglialatela M. Retigabine and flupirtine exert neuroprotective actions in organotypic hippocampal cultures. Neuropharmacology. 2006;51(2):283-294.
30. Otto M, Cepek L, Ratzka P, et al. Efficacy of flupirtine on cognitive function in patients with CJD: A double blind study. Neurology. 2004;62(5):714-718.
31. Friedel HA, Fitton A. Flupirtine. A review of its pharmacological properties, and therapeutic efficacy in pain states. Drugs. 1993;45(4): 548-569.
32. Porter RJ, Nohria V, Rundfeldt C. Retigabine. Neurotherapeutics. 2007; 4(1):149-154.
33. + channels in neuronal cells. Eur J Pharmacol. 1997;336(2-3):243-249.
34. + channel opening effect of the anticonvulsant retigabine in PC12 cells. Epilepsy Res. 1999;35(2): 99-107.
35. Rundfeldt C, Netzer R. The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells tranfected with human KCNQ2/3 subunits. Neurosci Lett. 2000;282(1-2):73-76.
36. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA. Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Mol Pharmacol. 2000;58(2):253-262.
37. Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK. Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol. 2000;58(3):591-600.
38. Gassen M, Pergande G, Youdim MB. Antioxidant properties of the triaminopyridine, flupirtine. Biochem Pharmacol. 1998;56(10): 1323-1329.
39. Tatulian L, Delmas P, Abogadie FC, Brown DA. Activation of expressed KCNQ potassium currents and native neuronal M-type potassium cur- rents by the anti-convulsant drug retigabine. J Neurosci. 2001;21(15): 5535-5545.
40. Dupuis DS, Schrøder RL, Jespersen T, et al. Activation of KCNQ5 channels stably expressed in HEK293 cells by BMS-204352. Eur J Pharmacol. 2002;437(3):129-137.
41. Soldovieri MV, Miceli F, Bellini G, Coppola G, Pascotto A, Taglialatela M. Correlating the clinical and genetic features of benign familial neonatal seizures (BFNS) with the functional consequences of underlying mutations. Channels. 2007;1(4):228-233.
42. Peretz A, Degani N, Nachman R, et al. Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol. 2005;67(4):1053-1066.
43. Peretz A, Sheinin A, Yue C, et al. Pre- and postsynaptic activation of M-channels by a novel opener dampens neuronal firing and transmitter release. J Neurophysiol. 2007;97(1):283-295.
44. Peretz A, Degani-Katzav N, Talmon M, et al. A tale of switched func- tions: From cyclooxygenase inhibition to M-channel modulation in new diphenylamine derivatives. PLoS One. 2007;2(12):e1332.
45. Wickenden AD, Krajewski JL, London B, et al. N-(6-chloro-pyridin- 3-yl)-3,4-difluoro-benzamide (ICA-27243): A novel, selective KCNQ2/Q3 potassium channel activator. Mol Pharmacol. 2008;73(3): 977-986.
46. Roeloffs R, Wickenden AD, Crean C, et al. In vivo profile of ICA- 27243 [N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide], a potent and selective KCNQ2/Q3 (Kv7.2/Kv7.3) activator in rodent anticonvulsant models. J Pharmacol Exp Ther. 2000;326(3):818-828.
47. Xiong Q, Sun H, Li M. Zinc pyrithione-mediated activation of voltage- gated KCNQ potassium channels rescues epileptogenic mutants. Nat Chem Biol. 2007;3(5):287-296.
48. Xiong Q, Sun H, Zhang Y, Nan F, Li M. Combinatorial augmentation of voltage-gated KCNQ potassium channels by chemical openers. Proc Natl Acad Sci U S A. 2008;105(8):3128-3133.
49. Schrøder RL, Jespersen T, Christophersen P, Strøbaek D, Jensen BS, Olesen SP. KCNQ4 channel activation by BMS-204352 and retigabine. Neuropharmacology. 2001;40(7):888-898.
50. Korsgaard MP, Hartz BP, Brown WD, Ahring PK, Strobaek D, Mirza NR. Anxiolytic effects of maxipost (BMS-204352) and retigabine via activation of neuronal Kv7 channels. J Pharmacol Exp Ther. 2005; 314(1):282-292.
51. Bentzen BH, Schmitt N, Calloe K, Dalby Brown W, Grunnet M, Olesen SP. The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels. Neuropharmacology. 2006;51(6):1068-1077.
52. Wuttke TV, Seebohm G, Bail S, Maljevic S, Lerche H. The new anti- convulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. Mol Pharmacol. 2005;67(4):1009-1017.
53. + channel sensitivity to the anticonvulsant retigabine. J Neurosci. 2005;25(20):5051-5060.
54. + channels. Mol Pharmacol. 2009;75(2):272-280.
55. + channels with a new gating-modifier. Proc Natl Acad Sci U S A. 2010;107(35):15637-15642.
56. Padilla K, Wickenden AD, Gerlach AC, McCormack K. The KCNQ2/3 selective channel opener ICA-27243 binds to a novel voltage- sensor domain site. Neurosci Lett. 2009;465(2):138-142.
57. Rostock A, Tober C, Rundfeldt C, et al. D-23129: A new anticonvulsant with a broad spectrum activity in animal models of epileptic seizures. Epilepsy Res. 1996;23(3):211-223.
58. Dailey JW, Cheong JH, Ko KH, Adams-Curtis LE, Jobe PC. Anticonvulsant properties of D-20443 in genetically epilepsy-prone rats: Prediction of clinical response. Neurosci Lett. 1995;195(2):77-80.
59. de Sarro G, di Paola ED, Conte G, Pasculli MP, de Sarro A. Influence of retigabine on the anticonvulsant activity of some antiepileptic drugs against audiogenic seizures in DBA/2 mice. Naunyn Schmiedebergs Arch Pharmacol. 2001;363(3):330-336.
60. Tober C, Rostock A, Rundfeldt C, Bartsch R. D-23129: A potent anticonvulsant in the amygdala kindling model of complex partial seizures. Eur J Pharmacol. 1996;303(3):163-169.
61. Postma T, Krupp E, Li XL, Post RM, Weiss SR. Lamotrigine treat- ment during amygdala-kindled seizure development fails to inhibit seizures and diminishes subsequent anticonvulsant efficacy. Epilepsia. 2000;41(12):1514-1521.
62. Barton ME, Klein BD, Wolf HH, White HS. Pharmacological charac- terization of the 6 Hz psychomotor seizure model of partial epilepsy. Epilepsy Res. 2001;47(3):217-227.
63. Srivastava AK, White HS. Retigabine decreases behavioral and electro- graphic seizures in the lamotrigine-resistant amygdala kindled rat model of pharmacoresistant epilepsy. Epilepsia. 2005;46 Suppl 8:S217.
64. Smith MD, Adams AC, Saunders GW, White HS, Wilcox KS. Phenytoin- and carbamazepine-resistant spontaneous bursting in rat entorhinal cortex is blocked by retigabine in vitro. Epilepsy Res. 2007;74(2-3):97-106.
65. Straub H, Köhling R, Höhling J, et al. Effects of retigabine on rhyth- mic synchronous activity of human neocortical slices. Epilepsy Res. 2001;44(2-3):155-165.
66. Hiller A, Nguyen N, Strassburg CP, et al. Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999;27(5):605-612.
67. Ferron GM, Paul J, Fruncillo R, et al. Multiple-dose, linear, dose- proportional pharmacokinetics of retigabine in healthy volunteers. J Clin Pharmacol. 2002;42(2):175-182.
68. Hermann R, Ferron GM, Erb K, et al. Effects of age and sex on the disposition of retigabine. Clin Pharmacol Ther. 2003;73(1):61-70.
69. Hermann R, Borlak J, Munzel U, et al. The role of Gilbert's syndrome and frequent NAT2 slow acetylation polymorphisms in the pharma- cokinetics of retigabine. Pharmacogenomics J. 2006;6(3):211-219.
70. Borlak J, Gasparic A, Locher M, Schupke H, Hermann R. N-Glucuroni- dation of the antiepileptic drug retigabine: Results from studies with human volunteers, heterologously expressed human UGTs, human liver, kidney, and liver microsomal membranes of Crigler-Najjar type II. Metabolism. 2006;55(6):711-721.
71. Ferron GM, Patat A, Parks V, Rolan P, Troy SM. Lack of pharmacoki- netic interaction between retigabine and phenobarbitone at steady-state in healthy subjects. Br J Clin Pharmacol. 2003;56(1):39-45.
72. Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: A summary of the Ninth EILAT Conference (EILAT IX). Epilepsy Res. 2009;83(1):1-43.
73. Hermann R, Knebel NG, Niebch G, Richards L, Borlak J, Locher M. Pharmacokinetic interaction between retigabine and lamotrigine in healthy subjects. Eur J Clin Pharmacol. 2003;58(12):795-802.
74. Porter RJ, Partiot A, Sachdeo R, Nohria V, Alves WM; for 205 Study Group. Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures. Neurology. 2007;68(15):1197-1204.
75. Bialer M, Johannessen SI, Kupferberg HJ, Levy RH, Perucca E, Tomson T. Progress report on new antiepileptic drugs: A summary of the Seventh EILAT Conference (EILAT VII). Epilepsy Res. 2004; 61(1-3):1-48.
76. Porter RJ, Nohria V, Pechstein B. Efficacy, safety, and tolerability of retigabine as adjunctive therapy in patients with refractory partial-onset seizures in an open-label study. Epilepsia. 2004;45 Suppl 7:S311.
77. Rode F, Svalø J, Sheykhzade M, Rønn LC. Functional effects of the KCNQ modulators retigabine and XE991 in the rat urinary bladder. Eur J Pharmacol. 2010;638(1-3):121-127.
78. Advisory Committee. Potiga™ (ezogabine) tablets as adjunctive therapy for the treatment of partial onset seizures. Peripheral and central nervous system drugs. Valeant Pharmaceuticals. 2010 Aug 11. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PeripheralandCentralNervousSystemDrugsAdvisoryCommittee/UCM222587.pdf. Accessed 2010 Nov 8.
79. Pati S, Alexopoulos AV. Pharmacoresistant epilepsy: From patho- genesis to current and emerging therapies. Cleve Clin J Med. 2010; 77(7):457-467.
80. Hermann B, Seidenberg M. Epilepsy and cognition. Epilepsy Curr. 2007;7(1):1-6.
81. Kanner AM, Balabanov A. Depression and epilepsy: How closely related are they? Neurology. 2002;58(8 Suppl 5):S2-S39.
82. Kwan P, Sperling MR. Refractory seizures: Try additional antiepileptic drugs (after two have failed) or go directly to early surgery evaluation? Epilepsia. 2009; 50 Suppl 8: S57-S62.
83. Brodie MJ. Do we need any more new antiepileptic drugs? Epilepsy Res. 2001;45(1-3):3-6.
84. Okada M, Zhu G, Hirose S, et al. Age-dependent modulation of hippocampal excitability by KCNQ-channels. Epilepsy Res. 2003;53(1-2):81-94.
85. + M-current regulates the transition to seizures in immature and adult hippocampus. Epilepsia. 2007;48(11): 2047-2058.
86. Peña F, Alavez-Pérez N. Epileptiform activity induced by pharmaco- logic reduction of M-current in the developing hippocampus in vitro. Epilepsia. 2006;47(1):47-54.
87. Safiulina VF, Zacchi P, Taglialatela M, Yaari Y, Cherubini E. Low expression of Kv7/M channels facilitates intrinsic and network bursting in the developing rat hippocampus. J Physiol. 2008;586(22): 5437-5453.
88. Painter MJ, Sher MS, Stein AD, et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med. 1999;341(7):485-489.
89. Olney JW, Young C, Wozniak DF, Jevtovic-Todorovic V, Ikonomidou C. Do pediatric drugs cause developing neurons to commit suicide? Trends Pharmacol Sci. 2004;25(3):135-139.
90. Raol YH, Lapides DA, Keating JG, Brooks-Kayal AR, Cooper EC. A KCNQ channel opener for experimental neonatal seizures and status epilepticus. Ann Neurol. 2009;65(3):326-336.
91. Mazarati A, Wu J, Shin D, Kwon YS, Sankar R. Antiepileptogenic and antiictogenic effects of retigabine under conditions of rapid kindling: An ontogenic study. Epilepsia. 2008;49(10):1777-1786.
92. Miceli F, Soldovieri MV, Lugli L, et al. Neutralization of a unique, negatively-charged residue in the voltage sensor of Kv7.2 subunits in a sporadic case of benign familial neonatal seizures. Neurobiol Dis. 2009;34(3):501-510.
93. + channel in a lipid membrane-like environment. Nature. 2007;450(7168):376-382.