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Identification
Name Lamotrigine
Accession Number DB00555 (APRD00570)
Type small molecule
Groups approved
Description

Lamotrigine is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. For epilepsy it is used to treat partial seizures, primary and secondary tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome. Lamotrigine also acts as a mood stabilizer. It is the first medication since lithium granted Food and Drug Administration (FDA) approval for the maintenance treatment of bipolar type I. Chemically unrelated to other anticonvulsants, lamotrigine has relatively few side-effects and does not require blood monitoring. The exact way lamotrigine works is unknown. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • GW 273293
  • Lamotrigina [Spanish]
  • lamotrigine
  • Lamotriginum [Latin]
Brand names
  • Lamictal
  • Lamictal CD
  • Lamictal XR
  • Lamictin
Brand name mixtures Not Available
Categories
  • Antidepressants
  • Anticonvulsants
  • Analgesics
  • Calcium Channel Blockers
  • Antimanic Agents
  • Excitatory Amino Acid Antagonists
CAS number 84057-84-1
Weight Average: 256.091
Monoisotopic: 255.007850663
Chemical Formula C9H7Cl2N5
InChI Key InChIKey=PYZRQGJRPPTADH-UHFFFAOYSA-N
InChI
InChI=1S/C9H7Cl2N5/c10-5-3-1-2-4(6(5)11)7-8(12)14-9(13)16-15-7/h1-3H,(H4,12,13,14,16)
Plain Text
IUPAC Name
6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine
SMILES
NC1=NC(N)=C(N=N1)C1=C(Cl)C(Cl)=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzene and Derivatives
  • Halobenzenes
  • Triazines
Substructures
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Triazines
  • Imines
  • Cyanamides
Pharmacology
Indication For the adjunctive treatment of partial seizures in epilepsy and generalized seizures of Lennox-Gastaut syndrome. Also for the maintenance treatment of bipolar I disorder and depression.
Pharmacodynamics Lamotrigine, an antiepileptic drug (AED) of the phenyltriazine class, is chemically unrelated to existing antiepileptic drugs. Lamotrigine is also used in the treatment of depression and bipolar disorder. Lamotrigine is thought to exert its anticonvulsant effect by stabilizing presynaptic neuronal membranes. Lamotrigine inhibits sodium currents by selectively binding to the inactivated state of the sodium channel and subsequently suppresses the release of the excilatory amino acid, glutamate.
Mechanism of action One proposed mechanism of action of Lamotrigine, the relevance of which remains to be established in humans, involves an effect on sodium channels. in vitro pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels and/or calcium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate). Studies on lamotrigine show binding to sodium channels similar to local anesthetics.
Absorption 98%
Volume of distribution
  • 0.9 to 1.3 L/kg
Protein binding 55%
Metabolism

Hepatic

Enzyme Metabolite Reaction Km Vmax
UDP-glucuronosyltransferase 1-4 lamotrigine-2-N-glucuronide Glucuronidation
UDP-glucuronosyltransferase 1-3 lamotrigine-2-N-glucuronide Glucuronidation
Route of elimination Not Available
Half life 25 +/- 10 hours (healthy individuals); 42.9 hours (chronic renal failure)
Clearance
  • Apparent plasma cl=0.44 mL/min/kg [healthy volunteers taking single-dose LAMICTAL]
  • Apparent plasma cl=0.58 mL/min/kg [healthy volunteers taking multiple-dose LAMICTAL]
  • Apparent plasma cl=0.30 mL/min/kg [healthy volunteers taking valproate and single-dose LAMICTAL]
  • Apparent plasma cl=0.18 mL/min/kg [healthy volunteers taking valproate and multiple-dose LAMICTAL]
  • Apparent plasma cl=1.1 mL/min/kg [Patients with epilepsy taking carbamazepine, phenytoin, phenobarbital, or primidone plus valproate and single-dose LAMICTAL]
  • Apparent plasma cl=1.12 mL/min/kg [Patients with epilepsy taking carbamazepine, phenytoin, phenobarbital, or primidone plus valproate and multiple-dose LAMICTAL]
Toxicity LD50=250 (mg/kg) (in rat, mice); LD50>640 orally (mg/kg) (in rat, mice) (Sawyer). Symptoms of overdose include decreased level of consciousness, coma, delayed heartbeat, increased seizures, lack of coordination, and rolling eyeballs.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Glaxosmithkline
  • Aurobindo pharma ltd
  • Dr reddys laboratories ltd
  • Glenmark generics ltd
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Taro pharmaceutical industries ltd
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Zydus pharmaceuticals usa inc
  • Smithkline beecham corp
  • Smithkline beecham corp dba glaxosmithkline
  • Apotex inc
  • Cadista pharmaceuticals inc
  • Lupin ltd
  • Matrix laboratories ltd
  • Roxane laboratories inc
  • Torrent pharmaceuticals ltd
  • Upsher smith laboratories inc
  • Wockhardt ltd
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
LaMICtal Starter 98 25 (84)-100(14)mg Kit Box 556.69 USD box
LaMICtal XR 200 mg 24 Hour tablet 12.11 USD tablet
Lamictal xr 200 mg tablet 11.65 USD tablet
LaMICtal XR 100 mg 24 Hour tablet 11.36 USD tablet
Lamictal xr 100 mg tablet 10.92 USD tablet
Lamictal xr 50 mg tablet 10.2 USD tablet
Lamictal 200 mg tablet 7.44 USD tablet
Lamictal odt start kt (orange) 7.28 USD tablet
Lamictal xr start kit (orange) 7.28 USD tablet
Lamictal odt 200 mg tablet 6.95 USD tablet
Lamictal odt 100 mg tablet 5.82 USD tablet
Lamotrigine 200 mg tablet 5.78 USD tablet
LaMICtal 25 mg Chew Tabs 5.63 USD tab
Lamictal odt 50 mg tablet 5.46 USD tablet
Lamictal tab start kit (green) 5.46 USD tablet
Lamictal 150 mg tablet 5.38 USD tablet
Lamictal odt 25 mg tablet 5.1 USD tablet
Lamictal xr 25 mg tablet 5.1 USD tablet
Lamictal 100 mg tablet 4.72 USD tablet
Lamotrigine tablet starter kit 4.24 USD tablet
Lamotrigine 150 mg tablet 3.98 USD tablet
Lamictal 25 mg tablet 3.78 USD tablet
Lamotrigine 100 mg tablet 3.52 USD tablet
LamoTRIgine 25 mg Chew Tabs 3.33 USD tab
LamoTRIgine 5 mg Chew Tabs 3.18 USD tab
Lamotrigine 25 mg tablet 2.9 USD tablet
Apo-Lamotrigine 150 mg Tablet 1.31 USD tablet
Mylan-Lamotrigine 150 mg Tablet 1.31 USD tablet
Novo-Lamotrigine 150 mg Tablet 1.31 USD tablet
Pms-Lamotrigine 150 mg Tablet 1.31 USD tablet
Ratio-Lamotrigine 150 mg Tablet 1.31 USD tablet
Apo-Lamotrigine 100 mg Tablet 0.88 USD tablet
Mylan-Lamotrigine 100 mg Tablet 0.88 USD tablet
Novo-Lamotrigine 100 mg Tablet 0.88 USD tablet
Pms-Lamotrigine 100 mg Tablet 0.88 USD tablet
Ratio-Lamotrigine 100 mg Tablet 0.88 USD tablet
Apo-Lamotrigine 25 mg Tablet 0.22 USD tablet
Mylan-Lamotrigine 25 mg Tablet 0.22 USD tablet
Novo-Lamotrigine 25 mg Tablet 0.22 USD tablet
Pms-Lamotrigine 25 mg Tablet 0.22 USD tablet
Ratio-Lamotrigine 25 mg Tablet 0.22 USD tablet
Lamictal 5 mg Chewable Tablet 0.18 USD tablet
Patents
Country Patent Number Approved Expires
United States 5698226 1995-07-29 2012-07-29
Canada 2277722 2001-03-27 2012-01-29
Properties
State solid
Melting point 216-218 oC (uncorr)
Experimental Properties
Property Value Source
logP 2.5 PhysProp
Predicted Properties
Property Value Source
water solubility 4.88e-01 g/l ALOGPS
logP 1.87 ALOGPS
logP 1.93 ChemAxon Molconvert
logS -2.72 ALOGPS
pKa 19.22 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 90.71 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 66.62 ChemAxon Molconvert
polarizability 23.10 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Backonja M: Neuromodulating drugs for the symptomatic treatment of neuropathic pain. Curr Pain Headache Rep. 2004 Jun;8(3):212-6. Pubmed
  2. Barbosa L, Berk M, Vorster M: A double-blind, randomized, placebo-controlled trial of augmentation with lamotrigine or placebo in patients concomitantly treated with fluoxetine for resistant major depressive episodes. J Clin Psychiatry. 2003 Apr;64(4):403-7. Pubmed
  3. Jensen TS: Anticonvulsants in neuropathic pain: rationale and clinical evidence. Eur J Pain. 2002;6 Suppl A:61-8. Pubmed
  4. Pappagallo M: Newer antiepileptic drugs: possible uses in the treatment of neuropathic pain and migraine. Clin Ther. 2003 Oct;25(10):2506-38. Pubmed
  5. Tehrani SP, Daryaafzoon M, Bakhtiarian A, Ejtemaeemehr S, Sahraei H: The effects of lamotrigine on the acquisition and expression of morphine-induced place preference in mice. Pak J Biol Sci. 2009 Jan 1;12(1):33-9. Pubmed
External Links
Resource Link
KEGG Drug D00354 Link_out
PubChem Compound 3878 Link_out
PubChem Substance 46505408 Link_out
ChemSpider 3741 Link_out
BindingDB 50031299 Link_out
ChEBI 6367 Link_out
ChEMBL 6367 Link_out
Therapeutic Targets Database DAP000039 Link_out
PharmGKB PA450164 Link_out
Drug Product Database 2248232 Link_out
RxList http://www.rxlist.com/cgi/generic/lamotrigine.htm Link_out
Drugs.com http://www.drugs.com/cdi/lamotrigine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Lamotrigine Link_out
ATC Codes
  • N03AX09
AHFS Codes
  • 28:12.92
PDB Entries Not Available
FDA label show (3.2 MB)
MSDS show (28.6 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
Targets

1. Sodium channel protein type 2 subunit alpha

Pharmacological action: unknown
Actions: inhibitor

Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient

Organism class: human
UniProt ID: Q99250 Link_out
Gene: SCN2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Lipkind GM, Fozzard HA: Molecular modeling of local anesthetic drug binding by voltage-gated sodium channels. Mol Pharmacol. 2005 Dec;68(6):1611-22. Epub 2005 Sep 20. Pubmed
Enzymes

1. UDP-glucuronosyltransferase 1-4

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX- alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate

UniProt ID: P22310 Link_out
Gene: UGT1A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Argikar UA, Senekeo-Effenberger K, Larson EE, Tukey RH, Remmel RP: Studies on induction of lamotrigine metabolism in transgenic UGT1 mice. Xenobiotica. 2009 Nov;39(11):826-35. Pubmed
  2. Chen H, Yang K, Choi S, Fischer JH, Jeong H: Up-regulation of UDP-glucuronosyltransferase (UGT) 1A4 by 17beta-estradiol: a potential mechanism of increased lamotrigine elimination in pregnancy. Drug Metab Dispos. 2009 Sep;37(9):1841-7. Epub 2009 Jun 22. Pubmed
  3. Argikar UA, Remmel RP: Variation in glucuronidation of lamotrigine in human liver microsomes. Xenobiotica. 2009 May;39(5):355-63. Pubmed

2. UDP-glucuronosyltransferase 1-3

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds

UniProt ID: P35503 Link_out
Gene: UGT1A3 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Argikar UA, Remmel RP: Variation in glucuronidation of lamotrigine in human liver microsomes. Xenobiotica. 2009 May;39(5):355-63. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: substrate

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Luna-Tortos C, Fedrowitz M, Loscher W: Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology. 2008 Dec;55(8):1364-75. Epub 2008 Sep 11. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on August 10, 2011 10:29

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.