Top ▲


Disease ID:302
Associated with:5 targets


Drugs:  EBIO reduces epileptiform activity in hippocampal slices and reduces seizures in a mouse model; SKA-31, riluzole and its derivative SKA-19 show anticonvulsant activity in various seizure models in mice and rats.
Side effects:  Sedation and impairment of motor coordination at higher doses.
Therapeutic use:  KCa2 activators have been suggested as anticonvulsants.
References:  1,3-4,8,10
Role:  Enhanced expression of HCN1 in dentate gyrus granule cells of hippocampi of patients suffering from temporal lobe epilepsy.
References:  2,11
Mutations:  Kv8.2 is associated with 2 mutation. Click here for details
Role:  Mutation increases persistent current
References:  5-6
Mutations:  Nav1.3 is associated with 1 mutation. Click here for details
synaptic vesicle glycoprotein 2A
Role:  SV2A is a widely distributed CNS protein believed to be involved in the abnormal coordination of synaptic vesicle exocytosis and neurotransmitter release underlying pathological brain activity in epileptic seizure. The exact mechanism has yet to be defined.
Drugs:  levetiracetam and brivaracetam
References:  9,12-13


No ligand related data available for Epilepsy


Show »

1. Anderson NJ, Slough S, Watson WP. (2006) In vivo characterisation of the small-conductance KCa (SK) channel activator 1-ethyl-2-benzimidazolinone (1-EBIO) as a potential anticonvulsant. Eur J Pharmacol, 546 (1-3): 48-53. [PMID:16925994]

2. Bender RA, Soleymani SV, Brewster AL, Nguyen ST, Beck H, Mathern GW, Baram TZ. (2003) Enhanced expression of a specific hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) in surviving dentate gyrus granule cells of human and experimental epileptic hippocampus. J Neurosci, 23 (17): 6826-36. [PMID:12890777]

3. Blank T, Nijholt I, Kye MJ, Spiess J. (2004) Small conductance Ca2+-activated K+ channels as targets of CNS drug development. Curr Drug Targets CNS Neurol Disord, 3 (3): 161-7. [PMID:15180477]

4. Coleman N, Nguyen HM, Cao Z, Brown BM, Jenkins DP, Zolkowska D, Chen YJ, Tanaka BS, Goldin AL, Rogawski MA et al.. (2015) The riluzole derivative 2-amino-6-trifluoromethylthio-benzothiazole (SKA-19), a mixed KCa2 activator and NaV blocker, is a potent novel anticonvulsant. Neurotherapeutics, 12 (1): 234-49. [PMID:25256961]

5. Estacion M, Gasser A, Dib-Hajj SD, Waxman SG. (2010) A sodium channel mutation linked to epilepsy increases ramp and persistent current of Nav1.3 and induces hyperexcitability in hippocampal neurons. Exp Neurol, 224 (2): 362-8. [PMID:20420834]

6. Holland KD, Kearney JA, Glauser TA, Buck G, Keddache M, Blankston JR, Glaaser IW, Kass RS, Meisler MH. (2008) Mutation of sodium channel SCN3A in a patient with cryptogenic pediatric partial epilepsy. Neurosci Lett, 433 (1): 65-70. [PMID:18242854]

7. Jorge BS, Campbell CM, Miller AR, Rutter ED, Gurnett CA, Vanoye CG, George Jr AL, Kearney JA. (2011) Voltage-gated potassium channel KCNV2 (Kv8.2) contributes to epilepsy susceptibility. Proc Natl Acad Sci USA, 108 (13): 5443-8. [PMID:21402906]

8. Lappin SC, Dale TJ, Brown JT, Trezise DJ, Davies CH. (2005) Activation of SK channels inhibits epileptiform bursting in hippocampal CA3 neurons. Brain Res, 1065 (1-2): 37-46. [PMID:16336949]

9. Mendoza-Torreblanca JG, Vanoye-Carlo A, Phillips-Farfán BV, Carmona-Aparicio L, Gómez-Lira G. (2013) Synaptic vesicle protein 2A: basic facts and role in synaptic function. Eur J Neurosci, 38 (11): 3529-39. [PMID:24102679]

10. Sankaranarayanan A, Raman G, Busch C, Schultz T, Zimin PI, Hoyer J, Köhler R, Wulff H. (2009) Naphtho[1,2-d]thiazol-2-ylamine (SKA-31), a new activator of KCa2 and KCa3.1 potassium channels, potentiates the endothelium-derived hyperpolarizing factor response and lowers blood pressure. Mol Pharmacol, 75 (2): 281-95. [PMID:18955585]

11. Surges R, Kukley M, Brewster A, Rüschenschmidt C, Schramm J, Baram TZ, Beck H, Dietrich D. (2012) Hyperpolarization-activated cation current Ih of dentate gyrus granule cells is upregulated in human and rat temporal lobe epilepsy. Biochem Biophys Res Commun, 420 (1): 156-60. [PMID:22405820]

12. Vogl C, Tanifuji S, Danis B, Daniels V, Foerch P, Wolff C, Whalley BJ, Mochida S, Stephens GJ. (2015) Synaptic vesicle glycoprotein 2A modulates vesicular release and calcium channel function at peripheral sympathetic synapses. Eur J Neurosci, 41 (4): 398-409. [PMID:25484265]

13. von Rosenstiel P. (2007) Brivaracetam (UCB 34714). Neurotherapeutics, 4 (1): 84-7. [PMID:17199019]