Target Validation Information
Target ID T29303
Target Name Sodium channel
Target Type
Successful
Drug Potency against Target Carisbamate Drug Info IC50 = 69000 nM [552886]
Phenytoin Drug Info IC50 = 58000 nM [553224]
Bupivacaine Drug Info IC50 = 6800 nM [552336]
Zonisamide Drug Info Ki = 1 nM [552703]
5-Heptyl-5-phenyl-imidazolidine-2,4-dione Drug Info IC50 = 5000 nM [525483]
5-Hexyl-5-phenyl-imidazolidine-2,4-dione Drug Info IC50 = 13000 nM [525483]
LOMERIZINE Drug Info IC50 = 26 nM [525961]
SIPATRIGINE Drug Info IC50 = 5300 nM [525961]
PD-85639 Drug Info IC50 = 46 nM [525961]
LIDOFLAZINE Drug Info Ki = 77 nM [533974]
L-741742 Drug Info Ki = 1900 nM [525540]
Benzocaine Drug Info IC50 = 258000 nM [552253]
Levobupivacaine Drug Info IC50 = 10000 nM [552398]
U-92032 Drug Info IC50 = 360 nM [525864]
4-Biphenyl-4-yl-2-methyl-1H-imidazole Drug Info IC50 = 1460 nM [527102]
NS-7 Drug Info IC50 = 1000 nM [525961]
Indol-1-yl-propyl-pyridin-4-yl-amine Drug Info IC50 = 5500 nM [525961]
LUBELUZOLE Drug Info IC50 = 280 nM [525961]
Oxybuprocaine Drug Info IC50 = 6310 nM [553206]
Mepivacaine Drug Info IC50 = 149000 nM [553280]
2-Hexyl-4-(4-isobutyl-phenyl)-1H-imidazole Drug Info IC50 = 28 nM [527102]
4-Biphenyl-4-yl-2-hexyl-1H-imidazole Drug Info IC50 = 16 nM [527102]
2-(1-Pentyl-hexyl)-4-phenyl-1H-imidazole Drug Info IC50 = 86 nM [527102]
Ropivacaine Drug Info IC50 = 20600 nM [552336]
Permethrin Drug Info IC50 = 50000 nM [552196]
PD-85639 Drug Info Ki = 260 nM [533974]
SIPATRIGINE Drug Info IC50 = 17850 nM [526398]
2-Hydroxy-2-phenyl-nonanoic acid amide Drug Info IC50 = 9000 nM [525483]
5-Nonyl-5-phenyl-imidazolidine-2,4-dione Drug Info IC50 = 5000 nM [525483]
4-Biphenyl-4-yl-2-(1-propyl-butyl)-1H-imidazole Drug Info IC50 = 100 nM [527102]
4-Biphenyl-4-yl-2-(1-pentyl-hexyl)-1H-imidazole Drug Info IC50 = 8 nM [527102]
4-Biphenyl-4-yl-2-cyclohexylmethyl-1H-imidazole Drug Info IC50 = 70 nM [527102]
Ralfinamide Drug Info IC50 = 10000 nM [552504]
Action against Disease Model Phenytoin The results obtained by Huntingdon Research Centre participating in a blind trial of the micromass assay for the prediction of teratogenic potential are presented. Twenty-five coded compounds were tested without S-9 mix using a pre-agreed protocol; three compounds were later tested with S-9. The data were assessed for sensitivity, specificity and accuracy using three separate sets of criteria based on either concentration (the <500 m ug/ml rule (i) and the <50 m ug/ml rule (ii)) or specific inhibition of cell differentiation at relatively non-cytotoxic concentrations (the 2-fold rule (iii)). The best in vivo/in vitro correlation was obtained using the 2-fold rule; the <500 m ug/ml rule was the most sensitive but gave a high false positive rate and the <50 m ug/ml rule was of low overall accuracy (60%). It is suggested that selective inhibition of differentiation of one cell type and cytotoxicity at low dose levels may also indicate risk of embryo-foeto toxicity, a factor to be considered with the pharmacokinetics of the compound. The teratogens procarbazine, methotrexate and caffeine were not detected; diphenhydramine and furazolidone initially classified as non-teratogens in vivo, were predicted as teratogens by the micromass assay. [553066] Drug Info
References
Ref 552886Carisbamate, a novel neuromodulator, inhibits voltage-gated sodium channels and action potential firing of rat hippocampal neurons. Epilepsy Res. 2009 Jan;83(1):66-72. doi: 10.1016/j.eplepsyres.2008.09.006. Epub 2008 Nov 14.
Ref 553224Lamotrigine, phenytoin and carbamazepine interactions on the sodium current present in N4TG1 mouse neuroblastoma cells. J Pharmacol Exp Ther. 1993 Aug;266(2):829-35.
Ref 552336Differential effects of bupivacaine enantiomers, ropivacaine and lidocaine on up-regulation of cell surface voltage-dependent sodium channels in adrenal chromaffin cells. Brain Res. 2003 Mar 21;966(2):175-84.
Ref 552703Carbonic anhydrase inhibitors as anticonvulsant agents. Curr Top Med Chem. 2007;7(9):855-64.
Ref 553066In vitro micromass teratogen test: Results from a blind trial of 25 compounds. Toxicol In Vitro. 1990;4(4-5):623-6.
Ref 525483J Med Chem. 1999 May 6;42(9):1537-45.Comparative molecular field analysis of hydantoin binding to the neuronal voltage-dependent sodium channel.
Ref 525483J Med Chem. 1999 May 6;42(9):1537-45.Comparative molecular field analysis of hydantoin binding to the neuronal voltage-dependent sodium channel.
Ref 525961J Med Chem. 2001 Jan 18;44(2):115-37.Medicinal chemistry of neuronal voltage-gated sodium channel blockers.
Ref 525961J Med Chem. 2001 Jan 18;44(2):115-37.Medicinal chemistry of neuronal voltage-gated sodium channel blockers.
Ref 525961J Med Chem. 2001 Jan 18;44(2):115-37.Medicinal chemistry of neuronal voltage-gated sodium channel blockers.
Ref 533974J Med Chem. 1994 Jan 21;37(2):268-74.Synthesis and pharmacological evaluation of phenylacetamides as sodium-channel blockers.
Ref 525540J Med Chem. 1999 Jul 15;42(14):2706-15.1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1, 3-dihydroimidazol-2-one: a selective high-affinity antagonist for the human dopamine D(4) receptor with excellent selectivity over ion channels.
Ref 552253Inhibition of m3 muscarinic acetylcholine receptors by local anaesthetics. Br J Pharmacol. 2001 May;133(1):207-16.
Ref 552398Local anaesthetic sensitivities of cloned HERG channels from human heart: comparison with HERG/MiRP1 and HERG/MiRP1 T8A. Br J Anaesth. 2004 Jan;92(1):93-101.
Ref 525864J Med Chem. 2000 Sep 7;43(18):3372-6.Discovery of (2S)-1-(4-amino-2,3,5- trimethylphenoxy)-3-[4-[4-(4- fluorobenzyl)phenyl]-1-piperazinyl]-2-propanol dimethanesulfonate (SUN N8075): a dual Na(+) and Ca(2+) channel blocker with antioxidant activity.
Ref 527102Bioorg Med Chem Lett. 2004 Jul 5;14(13):3521-3.2-Alkyl-4-arylimidazoles: structurally novel sodium channel modulators.
Ref 525961J Med Chem. 2001 Jan 18;44(2):115-37.Medicinal chemistry of neuronal voltage-gated sodium channel blockers.
Ref 525961J Med Chem. 2001 Jan 18;44(2):115-37.Medicinal chemistry of neuronal voltage-gated sodium channel blockers.
Ref 525961J Med Chem. 2001 Jan 18;44(2):115-37.Medicinal chemistry of neuronal voltage-gated sodium channel blockers.
Ref 553206Non-specific actions of the non-peptide tachykinin receptor antagonists, CP-96,345, RP 67580 and SR 48968, on neurotransmission. Br J Pharmacol. 1994 Jan;111(1):179-84.
Ref 553280Fundamental properties of local anesthetics: half-maximal blocking concentrations for tonic block of Na+ and K+ channels in peripheral nerve. Anesth Analg. 1998 Oct;87(4):885-9.
Ref 527102Bioorg Med Chem Lett. 2004 Jul 5;14(13):3521-3.2-Alkyl-4-arylimidazoles: structurally novel sodium channel modulators.
Ref 527102Bioorg Med Chem Lett. 2004 Jul 5;14(13):3521-3.2-Alkyl-4-arylimidazoles: structurally novel sodium channel modulators.
Ref 527102Bioorg Med Chem Lett. 2004 Jul 5;14(13):3521-3.2-Alkyl-4-arylimidazoles: structurally novel sodium channel modulators.
Ref 552336Differential effects of bupivacaine enantiomers, ropivacaine and lidocaine on up-regulation of cell surface voltage-dependent sodium channels in adrenal chromaffin cells. Brain Res. 2003 Mar 21;966(2):175-84.
Ref 552196WIN 17317-3, a new high-affinity probe for voltage-gated sodium channels. Biochemistry. 1999 Aug 24;38(34):11137-46.
Ref 533974J Med Chem. 1994 Jan 21;37(2):268-74.Synthesis and pharmacological evaluation of phenylacetamides as sodium-channel blockers.
Ref 526398J Med Chem. 2002 Aug 15;45(17):3755-64.Synthesis and structure-activity relationships of 6,7-benzomorphan derivatives as use-dependent sodium channel blockers for the treatment of stroke.
Ref 525483J Med Chem. 1999 May 6;42(9):1537-45.Comparative molecular field analysis of hydantoin binding to the neuronal voltage-dependent sodium channel.
Ref 525483J Med Chem. 1999 May 6;42(9):1537-45.Comparative molecular field analysis of hydantoin binding to the neuronal voltage-dependent sodium channel.
Ref 527102Bioorg Med Chem Lett. 2004 Jul 5;14(13):3521-3.2-Alkyl-4-arylimidazoles: structurally novel sodium channel modulators.
Ref 527102Bioorg Med Chem Lett. 2004 Jul 5;14(13):3521-3.2-Alkyl-4-arylimidazoles: structurally novel sodium channel modulators.
Ref 527102Bioorg Med Chem Lett. 2004 Jul 5;14(13):3521-3.2-Alkyl-4-arylimidazoles: structurally novel sodium channel modulators.
Ref 552504The anti-nociceptive agent ralfinamide inhibits tetrodotoxin-resistant and tetrodotoxin-sensitive Na+ currents in dorsal root ganglion neurons. Eur J Pharmacol. 2005 Mar 14;510(3):197-208.

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