Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Lamotrigine Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-06-12
Last Updated: 2023-10-25
Lamotrigine is a phenyltriazine antiepileptic used to treat some types of epilepsy and bipolar I disorder. It can be found under the brand name Lamictal. It is used in the treatment of both epilepsy and as a mood stabilizer in bipolar disorder. Lamotrigine is the first medication since lithium granted Food and Drug Administration (FDA) approval for the maintenance treatment of bipolar type I. It is approved for use in more than 30 countries. The exact mechanism of action of lamotrigine is not fully elucidated, as it may exert cellular activities that contribute to its efficacy in a range of conditions. Although chemically unrelated, lamotrigine actions resemble those of phenytoin and carbamazepine, inhibiting voltage-sensitive sodium channels, stabilizing neuronal membranes, thereby modulating the release of presynaptic excitatory neurotransmitters. Lamotrigine likely acts by inhibiting sodium currents by selective binding to the inactive sodium channel, suppressing the release of the excitatory amino acid, glutamate. The mechanism of action of lamotrigine in reducing anticonvulsant activity is likely the same in managing bipolar disorder. Studies on lamotrigine have identified its binding to sodium channels in a fashion similar to local anesthetics, which could explain the demonstrated clinical benefit of lamotrigine in some neuropathic pain states. Some side effects of using lamotrigine may include headaches, drowsiness, aggression, and tremors.
References
Lamotrigine 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
Goa KL, Ross SR, Chrisp P: Lamotrigine. A review of its pharmacological properties and clinical efficacy in epilepsy. Drugs. 1993 Jul;46(1):152-76. doi: 10.2165/00003495-199346010-00009.
Pubmed: 7691504
Rogawski MA, Loscher W: The neurobiology of antiepileptic drugs. Nat Rev Neurosci. 2004 Jul;5(7):553-64. doi: 10.1038/nrn1430.
Pubmed: 15208697
Kong W, Po S, Yamagishi T, Ashen MD, Stetten G, Tomaselli GF: Isolation and characterization of the human gene encoding Ito: further diversity by alternative mRNA splicing. Am J Physiol. 1998 Dec;275(6):H1963-70. doi: 10.1152/ajpheart.1998.275.6.H1963.
Pubmed: 9843794
Kikuno R, Nagase T, Ishikawa K, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 1999 Jun 30;6(3):197-205. doi: 10.1093/dnares/6.3.197.
Pubmed: 10470851
Zhu XR, Wulf A, Schwarz M, Isbrandt D, Pongs O: Characterization of human Kv4.2 mediating a rapidly-inactivating transient voltage-sensitive K+ current. Receptors Channels. 1999;6(5):387-400.
Pubmed: 10551270
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
Puckett C, Gomez CM, Korenberg JR, Tung H, Meier TJ, Chen XN, Hood L: Molecular cloning and chromosomal localization of one of the human glutamate receptor genes. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7557-61. doi: 10.1073/pnas.88.17.7557.
Pubmed: 1652753
Potier MC, Spillantini MG, Carter NP: The human glutamate receptor cDNA GluR1: cloning, sequencing, expression and localization to chromosome 5. DNA Seq. 1992;2(4):211-8.
Pubmed: 1320959
Sun W, Ferrer-Montiel AV, Schinder AF, McPherson JP, Evans GA, Montal M: Molecular cloning, chromosomal mapping, and functional expression of human brain glutamate receptors. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1443-7. doi: 10.1073/pnas.89.4.1443.
Pubmed: 1311100
Sun W, Ferrer-Montiel AV, Montal M: Primary structure and functional expression of the AMPA/kainate receptor subunit 2 from human brain. Neuroreport. 1994 Jan 12;5(4):441-4. doi: 10.1097/00001756-199401120-00018.
Pubmed: 8003671
Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. doi: 10.1038/nature03466.
Pubmed: 15815621
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
Wei X, Walia V, Lin JC, Teer JK, Prickett TD, Gartner J, Davis S, Stemke-Hale K, Davies MA, Gershenwald JE, Robinson W, Robinson S, Rosenberg SA, Samuels Y: Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet. 2011 May;43(5):442-6. doi: 10.1038/ng.810. Epub 2011 Apr 15.
Pubmed: 21499247
Lemke JR, Lal D, Reinthaler EM, Steiner I, Nothnagel M, Alber M, Geider K, Laube B, Schwake M, Finsterwalder K, Franke A, Schilhabel M, Jahn JA, Muhle H, Boor R, Van Paesschen W, Caraballo R, Fejerman N, Weckhuysen S, De Jonghe P, Larsen J, Moller RS, Hjalgrim H, Addis L, Tang S, Hughes E, Pal DK, Veri K, Vaher U, Talvik T, Dimova P, Guerrero Lopez R, Serratosa JM, Linnankivi T, Lehesjoki AE, Ruf S, Wolff M, Buerki S, Wohlrab G, Kroell J, Datta AN, Fiedler B, Kurlemann G, Kluger G, Hahn A, Haberlandt DE, Kutzer C, Sperner J, Becker F, Weber YG, Feucht M, Steinbock H, Neophythou B, Ronen GM, Gruber-Sedlmayr U, Geldner J, Harvey RJ, Hoffmann P, Herms S, Altmuller J, Toliat MR, Thiele H, Nurnberg P, Wilhelm C, Stephani U, Helbig I, Lerche H, Zimprich F, Neubauer BA, Biskup S, von Spiczak S: Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. Nat Genet. 2013 Sep;45(9):1067-72. doi: 10.1038/ng.2728. Epub 2013 Aug 11.
Pubmed: 23933819
Yuan H, Hansen KB, Zhang J, Pierson TM, Markello TC, Fajardo KV, Holloman CM, Golas G, Adams DR, Boerkoel CF, Gahl WA, Traynelis SF: Functional analysis of a de novo GRIN2A missense mutation associated with early-onset epileptic encephalopathy. Nat Commun. 2014;5:3251. doi: 10.1038/ncomms4251.
Pubmed: 24504326
Ohba C, Shiina M, Tohyama J, Haginoya K, Lerman-Sagie T, Okamoto N, Blumkin L, Lev D, Mukaida S, Nozaki F, Uematsu M, Onuma A, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, Tanaka F, Kato M, Ogata K, Saitsu H, Matsumoto N: GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders. Epilepsia. 2015 Jun;56(6):841-8. doi: 10.1111/epi.12987. Epub 2015 Apr 10.
Pubmed: 25864721
Foldes RL, Rampersad V, Kamboj RK: Cloning and sequence analysis of cDNAs encoding human hippocampus N-methyl-D-aspartate receptor subunits: evidence for alternative RNA splicing. Gene. 1993 Sep 15;131(2):293-8. doi: 10.1016/0378-1119(93)90309-q.
Pubmed: 8406025
Karp SJ, Masu M, Eki T, Ozawa K, Nakanishi S: Molecular cloning and chromosomal localization of the key subunit of the human N-methyl-D-aspartate receptor. J Biol Chem. 1993 Feb 15;268(5):3728-33.
Pubmed: 7679115
Lin YJ, Bovetto S, Carver JM, Giordano T: Cloning of the cDNA for the human NMDA receptor NR2C subunit and its expression in the central nervous system and periphery. Brain Res Mol Brain Res. 1996 Dec 31;43(1-2):57-64.
Pubmed: 9037519
Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. doi: 10.1038/nature04689.
Pubmed: 16625196
Mandich P, Schito AM, Bellone E, Antonacci R, Finelli P, Rocchi M, Ajmar F: Mapping of the human NMDAR2B receptor subunit gene (GRIN2B) to chromosome 12p12. Genomics. 1994 Jul 1;22(1):216-8. doi: 10.1006/geno.1994.1366.
Pubmed: 7959773
Schito AM, Pizzuti A, Di Maria E, Schenone A, Ratti A, Defferrari R, Bellone E, Mancardi GL, Ajmar F, Mandich P: mRNA distribution in adult human brain of GRIN2B, a N-methyl-D-aspartate (NMDA) receptor subunit. Neurosci Lett. 1997 Dec 12;239(1):49-53. doi: 10.1016/s0304-3940(97)00853-7.
Pubmed: 9547169
Lemke JR, Hendrickx R, Geider K, Laube B, Schwake M, Harvey RJ, James VM, Pepler A, Steiner I, Hortnagel K, Neidhardt J, Ruf S, Wolff M, Bartholdi D, Caraballo R, Platzer K, Suls A, De Jonghe P, Biskup S, Weckhuysen S: GRIN2B mutations in West syndrome and intellectual disability with focal epilepsy. Ann Neurol. 2014 Jan;75(1):147-54. doi: 10.1002/ana.24073. Epub 2014 Jan 2.
Pubmed: 24272827
Li D, Yuan H, Ortiz-Gonzalez XR, Marsh ED, Tian L, McCormick EM, Kosobucki GJ, Chen W, Schulien AJ, Chiavacci R, Tankovic A, Naase C, Brueckner F, von Stulpnagel-Steinbeis C, Hu C, Kusumoto H, Hedrich UB, Elsen G, Hortnagel K, Aizenman E, Lemke JR, Hakonarson H, Traynelis SF, Falk MJ: GRIN2D Recurrent De Novo Dominant Mutation Causes a Severe Epileptic Encephalopathy Treatable with NMDA Receptor Channel Blockers. Am J Hum Genet. 2016 Oct 6;99(4):802-816. doi: 10.1016/j.ajhg.2016.07.013. Epub 2016 Sep 8.
Pubmed: 27616483
Hess SD, Daggett LP, Deal C, Lu CC, Johnson EC, Velicelebi G: Functional characterization of human N-methyl-D-aspartate subtype 1A/2D receptors. J Neurochem. 1998 Mar;70(3):1269-79. doi: 10.1046/j.1471-4159.1998.70031269.x.
Pubmed: 9489750
Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. doi: 10.1038/nature02399.
Pubmed: 15057824
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