Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Tocainide Sodium Channel Cardiac Muscle Relaxation Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-07-19
Last Updated: 2023-11-27
Tocainide is an orally active class 1b antiarrhythmic agent that interferes with cardiac sodium channels and typically used to treat ventricular arrhythmias. It is used to treat conditions including sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias. Tocainide is a primary amine analog of lidocaine with antiarrhythmic properties useful in the treatment of ventricular arrhythmias. Tocainide, like lidocaine, produces dose dependent decreases in sodium and potassium conductance, thereby decreasing the excitability of myocardial cells. In experimental animal models, the dose-related depression of sodium current is more pronounced in ischemic tissue than in normal tissue. Tocainide is a Class I antiarrhythmic compound with electrophysiologic properties in man similar to those of lidocaine, but dissimilar from quinidine, procainamide, and disopyramide.Tocainide binds preferentially to the inactive state of the sodium channels. The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers. It also possesses some anticholinergic and local anesthetic properties. Side effects of tocainide include nausea, vomiting, headaches, feeling dizzy, or feeling hot and flushed.
References
Tocainide Sodium Channel Cardiac Muscle Relaxation Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Tocainide.
Pubmed: 30000176
Holmes B, Brogden RN, Heel RC, Speight TM, Avery GS: Tocainide. A review of its pharmacological properties and therapeutic efficacy. Drugs. 1983 Aug;26(2):93-123. doi: 10.2165/00003495-198326020-00001.
Pubmed: 6411445
Bagattin A, Veronese C, Rampazzo A, Danieli GA: Gene symbol: RYR2. Disease: Effort-induced polymorphic ventricular arrhythmias. Hum Genet. 2004 Mar;114(4):404.
Pubmed: 15046072
Tunwell RE, Wickenden C, Bertrand BM, Shevchenko VI, Walsh MB, Allen PD, Lai FA: The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis. Biochem J. 1996 Sep 1;318 ( Pt 2):477-87. doi: 10.1042/bj3180477.
Pubmed: 8809036
Tiso N, Stephan DA, Nava A, Bagattin A, Devaney JM, Stanchi F, Larderet G, Brahmbhatt B, Brown K, Bauce B, Muriago M, Basso C, Thiene G, Danieli GA, Rampazzo A: Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet. 2001 Feb 1;10(3):189-94. doi: 10.1093/hmg/10.3.189.
Pubmed: 11159936
Giudicessi JR, Ye D, Tester DJ, Crotti L, Mugione A, Nesterenko VV, Albertson RM, Antzelevitch C, Schwartz PJ, Ackerman MJ: Transient outward current (I(to)) gain-of-function mutations in the KCND3-encoded Kv4.3 potassium channel and Brugada syndrome. Heart Rhythm. 2011 Jul;8(7):1024-32. doi: 10.1016/j.hrthm.2011.02.021. Epub 2011 Feb 22.
Pubmed: 21349352
Lee YC, Durr A, Majczenko K, Huang YH, Liu YC, Lien CC, Tsai PC, Ichikawa Y, Goto J, Monin ML, Li JZ, Chung MY, Mundwiller E, Shakkottai V, Liu TT, Tesson C, Lu YC, Brice A, Tsuji S, Burmeister M, Stevanin G, Soong BW: Mutations in KCND3 cause spinocerebellar ataxia type 22. Ann Neurol. 2012 Dec;72(6):859-69. doi: 10.1002/ana.23701.
Pubmed: 23280837
Kurihara M, Ishiura H, Sasaki T, Otsuka J, Hayashi T, Terao Y, Matsukawa T, Mitsui J, Kaneko J, Nishiyama K, Doi K, Yoshimura J, Morishita S, Shimizu J, Tsuji S: Novel De Novo KCND3 Mutation in a Japanese Patient with Intellectual Disability, Cerebellar Ataxia, Myoclonus, and Dystonia. Cerebellum. 2018 Apr;17(2):237-242. doi: 10.1007/s12311-017-0883-4.
Pubmed: 28895081
Bahring R, Dannenberg J, Peters HC, Leicher T, Pongs O, Isbrandt D: Conserved Kv4 N-terminal domain critical for effects of Kv channel-interacting protein 2.2 on channel expression and gating. J Biol Chem. 2001 Jun 29;276(26):23888-94. doi: 10.1074/jbc.M101320200. Epub 2001 Apr 3.
Pubmed: 11287421
An WF, Bowlby MR, Betty M, Cao J, Ling HP, Mendoza G, Hinson JW, Mattsson KI, Strassle BW, Trimmer JS, Rhodes KJ: Modulation of A-type potassium channels by a family of calcium sensors. Nature. 2000 Feb 3;403(6769):553-6. doi: 10.1038/35000592.
Pubmed: 10676964
Ohya S, Morohashi Y, Muraki K, Tomita T, Watanabe M, Iwatsubo T, Imaizumi Y: Molecular cloning and expression of the novel splice variants of K(+) channel-interacting protein 2. Biochem Biophys Res Commun. 2001 Mar 23;282(1):96-102. doi: 10.1006/bbrc.2001.4558.
Pubmed: 11263977
Tinel N, Diochot S, Lauritzen I, Barhanin J, Lazdunski M, Borsotto M: M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit. FEBS Lett. 2000 Sep 1;480(2-3):137-41. doi: 10.1016/s0014-5793(00)01918-9.
Pubmed: 11034315
Tinel N, Diochot S, Borsotto M, Lazdunski M, Barhanin J: KCNE2 confers background current characteristics to the cardiac KCNQ1 potassium channel. EMBO J. 2000 Dec 1;19(23):6326-30. doi: 10.1093/emboj/19.23.6326.
Pubmed: 11101505
Yang Y, Xia M, Jin Q, Bendahhou S, Shi J, Chen Y, Liang B, Lin J, Liu Y, Liu B, Zhou Q, Zhang D, Wang R, Ma N, Su X, Niu K, Pei Y, Xu W, Chen Z, Wan H, Cui J, Barhanin J, Chen Y: Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation. Am J Hum Genet. 2004 Nov;75(5):899-905. doi: 10.1086/425342. Epub 2004 Sep 13.
Pubmed: 15368194
Huffaker SJ, Chen J, Nicodemus KK, Sambataro F, Yang F, Mattay V, Lipska BK, Hyde TM, Song J, Rujescu D, Giegling I, Mayilyan K, Proust MJ, Soghoyan A, Caforio G, Callicott JH, Bertolino A, Meyer-Lindenberg A, Chang J, Ji Y, Egan MF, Goldberg TE, Kleinman JE, Lu B, Weinberger DR: A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia. Nat Med. 2009 May;15(5):509-18. doi: 10.1038/nm.1962. Epub 2009 May 3.
Pubmed: 19412172
Warmke JW, Ganetzky B: A family of potassium channel genes related to eag in Drosophila and mammals. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3438-42. doi: 10.1073/pnas.91.8.3438.
Pubmed: 8159766
Itoh T, Tanaka T, Nagai R, Kamiya T, Sawayama T, Nakayama T, Tomoike H, Sakurada H, Yazaki Y, Nakamura Y: Genomic organization and mutational analysis of HERG, a gene responsible for familial long QT syndrome. Hum Genet. 1998 Apr;102(4):435-9. doi: 10.1007/s004390050717.
Pubmed: 9600240
Kupershmidt S, Yang IC, Hayashi K, Wei J, Chanthaphaychith S, Petersen CI, Johns DC, George AL Jr, Roden DM, Balser JR: The IKr drug response is modulated by KCR1 in transfected cardiac and noncardiac cell lines. FASEB J. 2003 Dec;17(15):2263-5. doi: 10.1096/fj.02-1057fje. Epub 2003 Oct 2.
Pubmed: 14525949
Scherer SE, Muzny DM, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Montgomery KT, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Lovering RC, Wheeler DA, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Draper H, Gonzalez-Garay ML, Havlak P, Jackson LR, Jacob LS, Kelly SH, Li L, Li Z, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Pasternak S, Perez LM, Plopper FJ, Santibanez J, Shen H, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Zhang J, Zhou J, Allen CC, Amin AG, Anyalebechi V, Bailey M, Barbaria JA, Bimage KE, Bryant NP, Burch PE, Burkett CE, Burrell KL, Calderon E, Cardenas V, Carter K, Casias K, Cavazos I, Cavazos SR, Ceasar H, Chacko J, Chan SN, Chavez D, Christopoulos C, Chu J, Cockrell R, Cox CD, Dang M, Dathorne SR, David R, Davis CM, Davy-Carroll L, Deshazo DR, Donlin JE, D'Souza L, Eaves KA, Egan A, Emery-Cohen AJ, Escotto M, Flagg N, Forbes LD, Gabisi AM, Garza M, Hamilton C, Henderson N, Hernandez O, Hines S, Hogues ME, Huang M, Idlebird DG, Johnson R, Jolivet A, Jones S, Kagan R, King LM, Leal B, Lebow H, Lee S, LeVan JM, Lewis LC, London P, Lorensuhewa LM, Loulseged H, Lovett DA, Lucier A, Lucier RL, Ma J, Madu RC, Mapua P, Martindale AD, Martinez E, Massey E, Mawhiney S, Meador MG, Mendez S, Mercado C, Mercado IC, Merritt CE, Miner ZL, Minja E, Mitchell T, Mohabbat F, Mohabbat K, Montgomery B, Moore N, Morris S, Munidasa M, Ngo RN, Nguyen NB, Nickerson E, Nwaokelemeh OO, Nwokenkwo S, Obregon M, Oguh M, Oragunye N, Oviedo RJ, Parish BJ, Parker DN, Parrish J, Parks KL, Paul HA, Payton BA, Perez A, Perrin W, Pickens A, Primus EL, Pu LL, Puazo M, Quiles MM, Quiroz JB, Rabata D, Reeves K, Ruiz SJ, Shao H, Sisson I, Sonaike T, Sorelle RP, Sutton AE, Svatek AF, Svetz LA, Tamerisa KS, Taylor TR, Teague B, Thomas N, Thorn RD, Trejos ZY, Trevino BK, Ukegbu ON, Urban JB, Vasquez LI, Vera VA, Villasana DM, Wang L, Ward-Moore S, Warren JT, Wei X, White F, Williamson AL, Wleczyk R, Wooden HS, Wooden SH, Yen J, Yoon L, Yoon V, Zorrilla SE, Nelson D, Kucherlapati R, Weinstock G, Gibbs RA: The finished DNA sequence of human chromosome 12. Nature. 2006 Mar 16;440(7082):346-51. doi: 10.1038/nature04569.
Pubmed: 16541075
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Schmitt N, Schwarz M, Peretz A, Abitbol I, Attali B, Pongs O: A recessive C-terminal Jervell and Lange-Nielsen mutation of the KCNQ1 channel impairs subunit assembly. EMBO J. 2000 Feb 1;19(3):332-40. doi: 10.1093/emboj/19.3.332.
Pubmed: 10654932
Selyanko AA, Hadley JK, Wood IC, Abogadie FC, Jentsch TJ, Brown DA: Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors. J Physiol. 2000 Feb 1;522 Pt 3:349-55. doi: 10.1111/j.1469-7793.2000.t01-2-00349.x.
Pubmed: 10713961
Angelo K, Jespersen T, Grunnet M, Nielsen MS, Klaerke DA, Olesen SP: KCNE5 induces time- and voltage-dependent modulation of the KCNQ1 current. Biophys J. 2002 Oct;83(4):1997-2006. doi: 10.1016/S0006-3495(02)73961-1.
Pubmed: 12324418
Kang C, Tian C, Sonnichsen FD, Smith JA, Meiler J, George AL Jr, Vanoye CG, Kim HJ, Sanders CR: Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel. Biochemistry. 2008 Aug 5;47(31):7999-8006. doi: 10.1021/bi800875q. Epub 2008 Jul 9.
Pubmed: 18611041
Tesson F, Donger C, Denjoy I, Berthet M, Bennaceur M, Petit C, Coumel P, Schwarts K, Guicheney P: Exclusion of KCNE1 (IsK) as a candidate gene for Jervell and Lange-Nielsen syndrome. J Mol Cell Cardiol. 1996 Sep;28(9):2051-5.
Pubmed: 8899564
Schulze-Bahr E, Wang Q, Wedekind H, Haverkamp W, Chen Q, Sun Y, Rubie C, Hordt M, Towbin JA, Borggrefe M, Assmann G, Qu X, Somberg JC, Breithardt G, Oberti C, Funke H: KCNE1 mutations cause jervell and Lange-Nielsen syndrome. Nat Genet. 1997 Nov;17(3):267-8. doi: 10.1038/ng1197-267.
Pubmed: 9354783
Schmid D, Stolzlechner M, Sorgner A, Bentele C, Assinger A, Chiba P, Moeslinger T: An abundant, truncated human sulfonylurea receptor 1 splice variant has prodiabetic properties and impairs sulfonylurea action. Cell Mol Life Sci. 2012 Jan;69(1):129-48. doi: 10.1007/s00018-011-0739-x. Epub 2011 Jun 14.
Pubmed: 21671119
Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. doi: 10.1038/nature04632.
Pubmed: 16554811
Thomas PM, Cote GJ, Wohllk N, Haddad B, Mathew PM, Rabl W, Aguilar-Bryan L, Gagel RF, Bryan J: Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science. 1995 Apr 21;268(5209):426-9. doi: 10.1126/science.7716548.
Pubmed: 7716548
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings