Details of the Drug-Related molecule(s) Interaction Atlas

General Information of DTT (ID: TTRK8B9)

• DTT Name: Sodium channel unspecific (NaC) DTT Info
• Gene Name: NaC

Molecule-Related Drug & Molecule List

18 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Benzocaine	DMI18HW	Anaesthesia	9A78.6	Approved	[1]
Butacaine	DM584TM	Pain	MG30-MG3Z	Approved	[2]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[3]
Eslicarbazepine	DMZREFQ	Seizure disorder	8A6Z	Approved	[4]
Levobupivacaine	DM783CH	Anaesthesia	9A78.6	Approved	[5]
LIDOFLAZINE	DMV23GL	Angina pectoris	BA40	Approved	[6]
LOMERIZINE	DME0TC8	Migraine	8A80	Approved	[7]
Mepivacaine	DMH2NMY	Analgesia	MB40.8	Approved	[5]
Oxybuprocaine	DMI0GDH	Anaesthesia	9A78.6	Approved	[8]
Pachycarpine	DMNKT8Z	Postpartum haemorrhage	JA43	Approved	[9]
Permethrin	DMZ0Q1G	Pediculus capitis infestation	1G00.0	Approved	[10]
Phenacemide	DMOHS9P	Epilepsy	8A60-8A68	Approved	[11]
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[12]
Pilsicainide	DMZ65K8	Heart arrhythmia	BC65	Approved	[13]
Pirmenol	DMBCYF5	Heart arrhythmia	BC65	Approved	[14]
Rufinamide	DMWE60C	Epilepsy	8A60-8A68	Approved	[15]
Tetrodotoxin	DMWMPRG	Bacterial infection	1A00-1C4Z	Approved	[16]
Zonisamide	DM0DTF7	Alcohol dependence	6C40.2	Approved	[17]

16 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Carisbamate	DM4Y1SP	Epilepsy	8A60-8A68	Phase 3	[4]
Ralfinamide	DMUNMY0	Neuropathic pain	8E43.0	Phase 3	[18]
ATI-2042	DMWP59B	Atrial fibrillation	BC81.3	Phase 2	[19]
BN82451	DMUM2KA	Parkinson disease	8A00.0	Phase 2	[20]
COL-1077	DMNC76I	Pain	MG30-MG3Z	Phase 2	[21]
Crobenetine	DM85WID	Pain	MG30-MG3Z	Phase 2	[22]
GSK2339345	DMRA3T2	Cough	MD12	Phase 2	[23]
HBI-3000	DM74ZKN	Heart arrhythmia	BC65	Phase 2	[24]
NS-7	DM3H82Q	Nerve injury	ND56.4	Phase 2	[25]
NW-3509	DM2UJ1H	Schizophrenia	6A20	Phase 2	[26]
Phenylbutyrate	DMBHPDW	Urea cycle disorder	5C50.A	Phase 2	[27]
SMP-986	DMTJOQX	Overactive bladder	GC50.0	Phase 2	[28]
P-552-02	DM6V5OB	Cystic fibrosis	CA25	Phase 1/2	[29]
ADCI	DM59EUY	Epileptic seizures	8A61-8A6Z	Phase 1	[30]
AZD-3161	DMICW7D	Peripheral neuropathy	8C0Z	Phase 1	[31]
BDD-10103	DMGAP53	Pain	MG30-MG3Z	Phase 1	[32]

35 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LUBELUZOLE	DMFGMD9	Neurological disorder	6B60	Discontinued in Preregistration	[7]
Bidisomide	DM47ZHW	Heart arrhythmia	BC65	Discontinued in Phase 3	[33]
Licarbazepine	DMWUS8N	Bipolar disorder	6A60	Discontinued in Phase 3	[34]
4030W92	DMQV4C3	Pain	MG30-MG3Z	Discontinued in Phase 2	[35]
4991W93	DMUXMGN	Migraine	8A80	Discontinued in Phase 2	[36]
534U87	DMYOG98	Epileptic seizures	8A61-8A6Z	Discontinued in Phase 2	[37]
Levosemotiadil	DMKSY2R	Cardiac arrhythmias	BC9Z	Discontinued in Phase 2	[38]
Org-7797	DMU5PFD	Cardiac arrhythmias	BC9Z	Discontinued in Phase 2	[39]
Pentisomide	DMTGBPW	Heart arrhythmia	BC65	Discontinued in Phase 2	[40]
Pyrazinoylguanidine	DMD308S	Diabetic complication	5A2Y	Discontinued in Phase 2	[41]
RSD-921	DMIKUXN	Anaesthesia	9A78.6	Discontinued in Phase 2	[42]
SILPERISONE HYDROCHLORIDE	DMY30G2	Spasm	MB47.3	Discontinued in Phase 2	[43]
SIPATRIGINE	DMMQ4GC	Neurological disorder	6B60	Discontinued in Phase 2	[7]
SOLPECAINOL HYDROCHLORIDE	DMHITR4	Cardiac arrhythmias	BC9Z	Discontinued in Phase 2	[44]
AMELTOLIDE	DMALVX2	Epileptic seizures	8A61-8A6Z	Discontinued in Phase 1	[45]
Artilide	DMJDYBX	Cardiac arrhythmias	BC9Z	Discontinued in Phase 1	[46]
AWD-140-190	DMTG9EZ	Epileptic seizures	8A61-8A6Z	Discontinued in Phase 1	[47]
SL-90.0571	DMFUTHB	Epilepsy	8A60-8A68	Discontinued in Phase 1	[48]
A-76895	DMTF6D9	Epilepsy	8A60-8A68	Terminated	[49]
AM-66	DMGBT63	Pain	MG30-MG3Z	Terminated	[49]
BDF-9148	DMV5K0I	Cardiac failure	BD10-BD13	Terminated	[50]
Berlafenone	DMQA4JU	Heart arrhythmia	BC65	Terminated	[48]
BW-1003C87	DMEP9B6	Cerebrovascular ischaemia	8B1Z	Terminated	[51]
DPI-201-106	DM1AQVE	Cardiovascular disease	BA00-BE2Z	Terminated	[52]
E-2070	DMAU0FP	Neuropathic pain	8E43.0	Terminated	[53]
GE-68	DMZF9CY	Heart arrhythmia	BC65	Terminated	[54]
PD-85639	DMNUKB4	N. A.	N. A.	Terminated	[7]
R-59494	DM36JFP	Ischemia	8B10-8B11	Terminated	[55]
Ralitoline	DM7HAE9	Epilepsy	8A60-8A68	Terminated	[56]
Recainam	DMDC2E8	Heart arrhythmia	BC65	Terminated	[57]
RP-66055	DM09QLY	Cerebral infarction	8B11.5Z	Terminated	[58]
RS-2135	DMFJ0KC	Heart arrhythmia	BC65	Terminated	[59]
SRSC-355	DMFLPU5	Neuropathic pain	8E43.0	Terminated	[60]
U-54494A	DM4WUEP	Epilepsy	8A60-8A68	Terminated	[61]
U-92032	DMTYO3P	N. A.	N. A.	Terminated	[62]

15 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-(1-Pentyl-hexyl)-4-phenyl-1H-imidazole	DMR0HDF	Discovery agent	N.A.	Investigative	[63]
2-Hexyl-4-(4-isobutyl-phenyl)-1H-imidazole	DM94PBL	Discovery agent	N.A.	Investigative	[63]
2-Hydroxy-2-phenyl-nonanoic acid amide	DM2GPF6	Discovery agent	N.A.	Investigative	[64]
4-Biphenyl-4-yl-2-(1-pentyl-hexyl)-1H-imidazole	DML6PTX	Discovery agent	N.A.	Investigative	[63]
4-Biphenyl-4-yl-2-(1-propyl-butyl)-1H-imidazole	DM2I13S	Discovery agent	N.A.	Investigative	[63]
4-Biphenyl-4-yl-2-cyclohexylmethyl-1H-imidazole	DMLSUXD	Discovery agent	N.A.	Investigative	[63]
4-Biphenyl-4-yl-2-hexyl-1H-imidazole	DMPIH4L	Discovery agent	N.A.	Investigative	[63]
4-Biphenyl-4-yl-2-methyl-1H-imidazole	DMNLC2Y	Discovery agent	N.A.	Investigative	[63]
5-Ethyl-3-methyl-5-phenyl-oxazolidine-2,4-dione	DMYD8GP	Discovery agent	N.A.	Investigative	[65]
5-Heptyl-5-phenyl-imidazolidine-2,4-dione	DMICKOU	Discovery agent	N.A.	Investigative	[64]
5-Hexyl-5-phenyl-imidazolidine-2,4-dione	DMCDUO1	Discovery agent	N.A.	Investigative	[64]
5-Nonyl-5-phenyl-imidazolidine-2,4-dione	DM2DWUQ	Discovery agent	N.A.	Investigative	[64]
BW-202W92	DMFKXMT	Discovery agent	N.A.	Investigative	[66]
L-741742	DMP75YK	Discovery agent	N.A.	Investigative	[67]
Saxitoxin	DMLX8RW	Discovery agent	N.A.	Investigative	[68]

References

• [1] Electrostatic contributions of aromatic residues in the local anesthetic receptor of voltage-gated sodium channels. Circ Res. 2008 Jan 4;102(1):86-94.
• [2] WO patent application no. 2008,0857,11, Synergy of sodium channel blockers and calcium channel blockers.
• [3] Sidedness of carbamazepine accessibility to voltage-gated sodium channels. Mol Pharmacol. 2014 Feb;85(2):381-7.
• [4] Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX). Epilepsy Res. 2009 Jan;83(1):1-43.
• [5] Block of neuronal tetrodotoxin-resistant Na+ currents by stereoisomers of piperidine local anesthetics. Anesth Analg. 2000 Dec;91(6):1499-505.
• [6] Synthesis and pharmacological evaluation of phenylacetamides as sodium-channel blockers. J Med Chem. 1994 Jan 21;37(2):268-74.
• [7] Medicinal chemistry of neuronal voltage-gated sodium channel blockers. J Med Chem. 2001 Jan 18;44(2):115-37.
• [8] Intrathecal oxybuprocaine and proxymetacaine produced potent and long-lasting spinal anesthesia in rats. Neurosci Lett. 2009 May 1;454(3):249-53.
• [9] Medicinal plants in therapy. Bull World Health Organ. 1985;63(6):965-81.
• [10] In vitro assays for repellents and deterrents for ticks: differing effects of products when tested with attractant or arrestment stimuli. Med Vet Entomol. 2003 Dec;17(4):370-8.
• [11] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [12] Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders. CNS Drugs. 2009;23(7):555-68.
• [13] A sodium channel blocker, pilsicainide, produces atrial post-repolarization refractoriness through the reduction of sodium channel availability. Tohoku J Exp Med. 2011;225(1):35-42.
• [14] Pirmenol, a new antiarrhythmic drug with potassium- and sodium-channel blocking activity; a voltage-clamp study in rabbit Purkinje fibres. Naunyn Schmiedebergs Arch Pharmacol. 1990 May;341(5):462-71.
• [15] Emerging drugs for epilepsy. Expert Opin Emerg Drugs. 2007 Sep;12(3):407-22.
• [16] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [17] Antiepileptic drugs and relapse after epilepsy surgery. Epileptic Disord. 2008 Sep;10(3):193-8.
• [18] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [19] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [20] Emerging drug therapies in Huntington's disease. Expert Opin Emerg Drugs. 2009 Jun;14(2):273-97.
• [21] Clinical pipeline report, company report or official report of Columbia Laboratories.
• [22] Analgesic activity of a novel use-dependent sodium channel blocker, crobenetine, in mono-arthritic rats. Br J Pharmacol. 2001 Dec;134(8):1742-8.
• [23] ClinicalTrials.gov (NCT01494636) The Safety, Tolerability, PK and PD of GSK2339345 in Healthy Subjects. U.S. National Institutes of Health.
• [24] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [25] Preferential inhibition by a novel Na(+)/Ca(2+) channel blocker NS-7 of severe to mild hypoxic injury in rat cerebrocortical slices: A possible involvement of a highly voltage-dependent blockade of Ca(2+) channel. J Pharmacol Exp Ther. 2000 May;293(2):522-9.
• [26] Clinical pipeline report, company report or official report of Newron.
• [27] Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
• [28] DUAL INHIBITION OF Na+-CHANNEL AND MUSCARINIC RECEPTORS BY SMP-986 EFFICIENTLY IMPROVED VOIDING FUNCTION COMPARED TO ANTI-MUSCARINIC AGENTS IN TWO CONSCIOUS RAT MODELS OF DETRUSOR OVERACTIVITY. The Journal of Urology Volume 179, Issue 4, Supplement, April 2008, Pages 129.
• [29] US patent application no. 2014,0221,286, Sodium channel blockers reduce glucagon secretion.
• [30] The anticonvulsant SGB-017 (ADCI) blocks voltage-gated sodium channels in rat and human neurons: comparison with carbamazepine. Epilepsia. 2000 Mar;41(3):263-70.
• [31] Recent progress in sodium channel modulators for pain.Bioorganic & Medicinal Chemistry Letters Volume 24, Issue 16, 15 August 2014, Pages 3690-3699.
• [32] Clinical pipeline report, company report or official report of Birds Pharma AG.
• [33] Bidisomide (SC-40230), a new antiarrhythmic agent: initial study of tolerability and pharmacokinetics. Clin Pharmacol Ther. 1992 Apr;51(4):371-8.
• [34] Emerging drugs for bipolar disorder. Expert Opin Emerg Drugs. 2006 Nov;11(4):621-34.
• [35] Lack of effect of two oral sodium channel antagonists, lamotrigine and 4030W92, on intradermal capsaicin-induced hyperalgesia model. Pharmacol Biochem Behav. 2004 Jun;78(2):349-55.
• [36] CGRP and its receptors provide new insights into migraine pathophysiology. Nat Rev Neurol. 2010 Oct;6(10):573-82.
• [37] The anticonvulsant BW534U87 depresses epileptiform activity in rat hippocampal slices by an adenosine-dependent mechanism and through inhibition of voltage-gated Na+ channels. Br J Pharmacol. 1999 Nov;128(5):1011-20.
• [38] Binding study of semotiadil and levosemotiadil with alpha(1)-acid glycoprotein using high-performance frontal analysis. Anal Biochem. 1999 Oct 1;274(1):27-33.
• [39] Electrophysiologic effects of Org 7797, a new steroidal antiarrhythmic agent: comparison with class 1a, 1b, and 1c drugs. J Cardiovasc Pharmacol. 1989 Aug;14(2):205-12.
• [40] Antiarrhythmic effect related to the plasma concentration of pentisomide in vivo and the antiarrhythmic-concentration relationship in vitro. Drugs Exp Clin Res. 1995;21(4):145-51.
• [41] Design, synthesis, and structure-activity relationships of novel 2-substituted pyrazinoylguanidine epithelial sodium channel blockers: drugs for cystic fibrosis and chronic bronchitis. J Med Chem. 2006 Jul 13;49(14):4098-115.
• [42] Molecular analysis of the Na+ channel blocking actions of the novel class I anti-arrhythmic agent RSD 921. Br J Pharmacol. 1999 May;127(1):9-18.
• [43] Tolperisone-type drugs inhibit spinal reflexes via blockade of voltage-gated sodium and calcium channels. J Pharmacol Exp Ther. 2005 Dec;315(3):1237-46.
• [44] US patent application no. 2002,0102,217, Diagnostic,therapeutic agents.
• [45] Synthesis and pharmacological evaluation of a major metabolite of ameltolide, a potent anticonvulsant. J Med Chem. 1991 Apr;34(4):1253-7.
• [46] Potassium channel blockers as antiarrhythmic drugs. Drug Development Research Volume 33, Issue 3, pages 235-249, November 1994.
• [47] Effects of AWD 140-190 on stimulus-induced field potentials and on different patterns of epileptiform activity induced by low calcium or low magnesium in rat entorhinal cortex hippocampal slices. Epilepsy Res. 1997 Dec;29(1):59-69.
• [48] WO patent application no. 19990639849, Novel sodium channel drugs and uses.
• [49] CA patent application no. 849505, Sodium channel blockers reduce glucagon secretion.
• [50] The relaxing effect of BDF 9148 on the KCl-contracted aorta isolated from normo- and hyper-tensive rats. Naunyn Schmiedebergs Arch Pharmacol. 1998 Feb;357(2):126-32.
• [51] The pyrimidine-derivative, BW1003C87, protects CA1 and striatal neurons following transient severe forebrain ischaemia in rats. A microdialysis and histological study. Neuroscience. 1993 Sep;56(1):93-9.
• [52] Interaction between DPI 201-106 enantiomers at the cardiac sodium channel. Mol Pharmacol. 1990 Jan;37(1):17-24.
• [53] Emerging therapies for neuropathic pain. Expert Opin Emerg Drugs. 2005 Feb;10(1):95-108.
• [54] Electrophysiological properties of the propafenone-analogue GE 68 (1-[3-(phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol) in isolated preparations and ventricular myocytes of guinea-pig hearts. Naunyn Schmiedebergs Arch Pharmacol. 1997 Feb;355(2):230-8.
• [55] Veratridine activates a silent sodium channel in rat isolated aorta. Eur J Pharmacol. 1992 Aug 25;219(2):253-9.
• [56] Anticonvulsant and sodium channel blocking effects of ralitoline in different screening models. Naunyn Schmiedebergs Arch Pharmacol. 1992 Oct;346(4):442-52.
• [57] Effects of renal function on recainam pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 1995 May;57(5):492-8.
• [58] Synthesis, anticonvulsant and neuroprotective activities of RP 66055, a riluzole derivative. Bioorg Med Chem. 1994 Aug;2(8):793-8.
• [59] Electrophysiologic effects of RS-2135, a new antiarrhythmic compound, on canine Purkinje fibers. J Cardiovasc Pharmacol. 1992 Dec;20(6):955-60.
• [60] WO patent application no. 2013,0439,25, Sodium channel blockers reduce glucagon secretion.
• [61] U-54494A: a unique anticonvulsant related to kappa opioid agonists. J Pharmacol Exp Ther. 1987 Nov;243(2):542-7.
• [62] Discovery of (2S)-1-(4-amino-2,3,5- trimethylphenoxy)-3-[4-[4-(4- fluorobenzyl)phenyl]-1-piperazinyl]-2-propanol dimethanesulfonate (SUN N8075): a ... J Med Chem. 2000 Sep 7;43(18):3372-6.
• [63] 2-Alkyl-4-arylimidazoles: structurally novel sodium channel modulators. Bioorg Med Chem Lett. 2004 Jul 5;14(13):3521-3.
• [64] Comparative molecular field analysis of hydantoin binding to the neuronal voltage-dependent sodium channel. J Med Chem. 1999 May 6;42(9):1537-45.
• [65] Sodium channel binding and anticonvulsant activities for the enantiomers of a bicyclic 2,4-oxazolidinedione and monocyclic models. J Med Chem. 1989 Jul;32(7):1577-80.
• [66] Oxadiazolylindazole sodium channel modulators are neuroprotective toward hippocampal neurones. J Med Chem. 2009 May 14;52(9):2694-707.
• [67] 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) rece... J Med Chem. 1999 Jul 15;42(14):2706-15.
• [68] Effect of neurotoxins on the electrical activity and contraction of the heart muscle. C R Seances Soc Biol Fil. 1997;191(3):451-71.