Lamotrigine
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Basic Info
| Common Name | Lamotrigine(F04720) |
| 2D Structure | |
| 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. |
| FRCD ID | F04720 |
| CAS Number | 84057-84-1 |
| PubChem CID | 3878 |
| Formula | C9H7Cl2N5 |
| IUPAC Name | 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine |
| InChI Key | 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) |
| Canonical SMILES | C1=CC(=C(C(=C1)Cl)Cl)C2=C(N=C(N=N2)N)N |
| Isomeric SMILES | C1=CC(=C(C(=C1)Cl)Cl)C2=C(N=C(N=N2)N)N |
| Wikipedia | Lamotrigine |
| Synonyms |
lamotrigine
84057-84-1
6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine
Lamictal
Lamictal Cd
Lamotrigina
Lamotriginum
Lamictal XR
Lamotriginum [Latin]
Lamotrigina [Spanish]
|
| Classifies |
Predicted: Pesticide
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Benzene and substituted derivatives |
| Subclass | Halobenzenes |
| Intermediate Tree Nodes | Chlorobenzenes |
| Direct Parent | Dichlorobenzenes |
| Alternative Parents | |
| Molecular Framework | Aromatic heteromonocyclic compounds |
| Substituents | 1,2-dichlorobenzene - Aminotriazine - Aryl chloride - Aryl halide - Triazine - Imidolactam - 1,2,4-triazine - Heteroaromatic compound - Organoheterocyclic compound - Azacycle - Amine - Primary amine - Organonitrogen compound - Organochloride - Organohalogen compound - Organopnictogen compound - Organic nitrogen compound - Hydrocarbon derivative - Aromatic heteromonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 256.09 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 1 |
| Complexity | 242 |
| Monoisotopic Mass | 255.008 |
| Exact Mass | 255.008 |
| XLogP | 1.4 |
| Formal Charge | 0 |
| Heavy Atom Count | 16 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9382 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2+ | 0.8867 |
| P-glycoprotein Substrate | Non-substrate | 0.7155 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9110 |
| Non-inhibitor | 0.9604 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8176 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.6315 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.9162 |
| CYP450 2D6 Substrate | Non-substrate | 0.9055 |
| CYP450 3A4 Substrate | Non-substrate | 0.6862 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.6110 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9071 |
| CYP450 2D6 Inhibitor | Inhibitor | 0.7007 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.8594 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.7678 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.5515 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9168 |
| Non-inhibitor | 0.8735 | |
| AMES Toxicity | Non AMES toxic | 0.8202 |
| Carcinogens | Non-carcinogens | 0.7895 |
| Fish Toxicity | High FHMT | 0.8228 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9747 |
| Honey Bee Toxicity | Low HBT | 0.8834 |
| Biodegradation | Not ready biodegradable | 1.0000 |
| Acute Oral Toxicity | II | 0.6525 |
| Carcinogenicity (Three-class) | Non-required | 0.5755 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.8245 | LogS |
| Caco-2 Permeability | 1.9162 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.7556 | LD50, mol/kg |
| Fish Toxicity | 1.3928 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.7650 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Therapeutic Index Estimation of Antiepileptic Drugs: A Systematic Literature Review Approach. | Clin Neuropharmacol | 2016 Sep-Oct | 27428884 |
| Mood stabilizers during breastfeeding: a systematic review of the recentliterature. | Bipolar Disord | 2016 Jun | 27297617 |
| Removal of triazine-based pollutants from water by carbon nanotubes: Impact ofdissolved organic matter (DOM) and solution chemistry. | Water Res | 2016 Dec 1 | 27710798 |
| Effect of cholecalciferol on the anticonvulsant action of some second generation antiepileptic drugs in the mouse model of maximal electroshock. | Pharmacol Rep | 2015 Oct | 26398379 |
| Effect of antiepileptic therapy on trace elements status in Indian population in a tertiary care hospital from northern India: a cross sectional study. | Epilepsy Res | 2014 Jul | 24679946 |
| Functional and structural evaluation of lamotrigine treatment in rat models ofacute and chronic ocular hypertension. | Exp Eye Res | 2013 Oct | 23810807 |
| Orally disintegrating tablet of novel salt of antiepileptic drug: formulationstrategy and evaluation. | Eur J Pharm Biopharm | 2013 Nov | 23800704 |
| Lamotrigine positively affects the development of psychiatric comorbidity inepileptic animals, while psychiatric comorbidity aggravates seizures. | Epilepsy Behav | 2013 Aug | 23773980 |
| Effects of lamotrigine on behavior, oxidative parameters and signaling cascadesin rats exposed to the chronic mild stress model. | Neurosci Res | 2013 Apr | 23416280 |
| VEGF regulates antidepressant effects of lamotrigine. | Eur Neuropsychopharmacol | 2012 Jun | 22033393 |
| Antimanic efficacy of retigabine in a proposed mouse model of bipolar disorder. | Behav Brain Res | 2010 Feb 11 | 19815032 |
| Plasma free carnitine in epilepsy children, adolescents and young adults treated with old and new antiepileptic drugs with or without ketogenic diet. | Brain Dev | 2006 Jul | 16376041 |
| Gestation-induced changes in lamotrigine pharmacokinetics: a monotherapy study. | Neurology | 2004 Aug 10 | 15304599 |
| Clinical pharmacology of topiramate versus lamotrigine versus phenobarbital:comparison of efficacy and side effects using odds ratios. | J Clin Pharmacol | 2003 May | 12751270 |
| Mood stabilizers during breastfeeding: a review. | J Clin Psychiatry | 2000 Feb | 10732654 |
| Newer antiepileptic drugs: gabapentin, lamotrigine, felbamate, topiramate andfosphenytoin. | Am Fam Physician | 1998 Feb 1 | 9475899 |
| Improvement of physicochemical properties of an antiepileptic drug by saltengineering. | None | None | 22588676 |
Targets
- General Function:
- Voltage-gated sodium channel activity
- Specific Function:
- 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.
- Gene Name:
- SCN1A
- Uniprot ID:
- P35498
- Molecular Weight:
- 228969.49 Da
- 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. <i>in vitro</i> pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate).
References
- Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
- General Function:
- Voltage-gated sodium channel activity
- Specific Function:
- 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.
- Gene Name:
- SCN3A
- Uniprot ID:
- Q9NY46
- Molecular Weight:
- 226291.905 Da
- 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. <i>in vitro</i> pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate).
References
- Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
- General Function:
- Voltage-gated sodium channel activity
- Specific Function:
- 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. In macrophages and melanoma cells, isoform 5 may participate in the control of podosome and invadopodia formation.
- Gene Name:
- SCN8A
- Uniprot ID:
- Q9UQD0
- Molecular Weight:
- 225278.005 Da
- 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. <i>in vitro</i> pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate).
References
- Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
- General Function:
- Voltage-gated sodium channel activity
- Specific Function:
- 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. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain (By similarity).
- Gene Name:
- SCN9A
- Uniprot ID:
- Q15858
- Molecular Weight:
- 226370.175 Da
- 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. <i>in vitro</i> pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate).
References
- Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
- General Function:
- Nadph binding
- Specific Function:
- Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
- Gene Name:
- DHFR
- Uniprot ID:
- P00374
- Molecular Weight:
- 21452.61 Da
- 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. <i>in vitro</i> pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate).
References
- Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
- General Function:
- Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
- Specific Function:
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
- Gene Name:
- KCNH2
- Uniprot ID:
- Q12809
- Molecular Weight:
- 126653.52 Da
References
- Coi A, Massarelli I, Testai L, Calderone V, Bianucci AM: Identification of "toxicophoric" features for predicting drug-induced QT interval prolongation. Eur J Med Chem. 2008 Nov;43(11):2479-88. doi: 10.1016/j.ejmech.2007.12.025. Epub 2008 Jan 5. [18262683 ]
- General Function:
- Voltage-gated sodium channel activity
- Specific Function:
- Tetrodotoxin-resistant channel that 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 sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.
- Gene Name:
- SCN10A
- Uniprot ID:
- Q9Y5Y9
- Molecular Weight:
- 220623.605 Da
References
- Drizin I, Gregg RJ, Scanio MJ, Shi L, Gross MF, Atkinson RN, Thomas JB, Johnson MS, Carroll WA, Marron BE, Chapman ML, Liu D, Krambis MJ, Shieh CC, Zhang X, Hernandez G, Gauvin DM, Mikusa JP, Zhu CZ, Joshi S, Honore P, Marsh KC, Roeloffs R, Werness S, Krafte DS, Jarvis MF, Faltynek CR, Kort ME: Discovery of potent furan piperazine sodium channel blockers for treatment of neuropathic pain. Bioorg Med Chem. 2008 Jun 15;16(12):6379-86. doi: 10.1016/j.bmc.2008.05.003. Epub 2008 May 6. [18501613 ]
- General Function:
- Voltage-gated sodium channel activity
- Specific Function:
- 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.
- Gene Name:
- SCN2A
- Uniprot ID:
- Q99250
- Molecular Weight:
- 227972.64 Da
- 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. <i>in vitro</i> pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate).
References
- Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
- General Function:
- Voltage-gated sodium channel activity involved in sa node cell action potential
- Specific Function:
- This protein 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. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
- Gene Name:
- SCN5A
- Uniprot ID:
- Q14524
- Molecular Weight:
- 226937.475 Da
- 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. <i>in vitro</i> pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate).
References
- Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
- General Function:
- Voltage-gated sodium channel activity
- Specific Function:
- This protein 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. This sodium channel may be present in both denervated and innervated skeletal muscle.
- Gene Name:
- SCN4A
- Uniprot ID:
- P35499
- Molecular Weight:
- 208059.175 Da
- 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. <i>in vitro</i> pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate).
References
- Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]