6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine

• ChemBase ID: 437
• Molecular Formular: C9H7Cl2N5
• Molecular Mass: 256.09138
• Monoisotopic Mass: 255.00785061
• SMILES: Clc1c(c2nnc(nc2N)N)cccc1Cl
• Canonical SMILES: Nc1nnc(c(n1)N)c1cccc(c1Cl)Cl
• 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)
• InChIKey: PYZRQGJRPPTADH-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine
• IUPAC Traditional name: lamotrigine; 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine
• Brand Name: Lamictal; Lamictal CD; Lamictin; Lamictal XR
• Synonyms: Lamotrigina [Spanish]; Lamotriginum [Latin]; GW 273293; lamotrigine; Lamotrigine; 3,5-Diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine; BW 430C; LTG; Lamictal; Lamictal XR; Lamotrigin; 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine; 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine; GI 267119X; Lamotrigine; Lamictin

Database IDs

• CAS Number: 84057-84-1
• EC Number: 281-901-8
• MDL Number: MFCD00865333
• PubChem SID: 24278792; 160963900; 46505408
• PubChem CID: 3878

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.979241
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): 1.4001383
• LogD (pH = 7.4): 1.9137787
• Log P: 1.9265221
• Molar Refractivity: 66.6197 cm^3
• Polarizability: 24.699194 Å^3
• Polar Surface Area: 90.71 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.87
• LOG S: -2.72
• Solubility (Water): 4.88e-01 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; DMSO: soluble20 mg/mL at 60 °C; Ethanol; H2O: insoluble; Methanol
• Apperance: white powder; White to Cream Coloured Solid
• Melting Point: 216-218°C
• Hydrophobicity(logP): 2.5; 2.534

Safety Information

• Storage Condition: -20°C Freezer
• RTECS: XY5850700
• European Hazard Symbols: Toxic (T)
• UN Number: 2811
• German water hazard class: 3
• Hazard Class: 6.1
• Packing Group: 3
• Risk Statements: 25
• Safety Statements: 45
• GHS Pictograms: GHS06
• GHS Signal Word: Danger
• GHS Hazard statements: H301
• GHS Precautionary statements: P301 + P310
• Personal Protective Equipment: Eyeshields, Faceshields, Gloves, type P2 (EN 143) respirator cartridges
• RID/ADR: UN 2811 6.1/PG 3
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: Sodium Channel
• Gene Information: human ... SCN5A(6331)rat ... Scn2a1(24766), Scnn1a(25122)
• Mechanism of Action: Inhibits release of excitatory amino acids via blockage of neuronal voltage-dependent sodium channels

Product Information

• Purity: ≥98%; 95%; 95+%
• Salt Data: Free Base
• Application(s): Anticonvulsant; Used in the treatment of epilepsy and bipolar disorder
• Empirical Formula (Hill Notation): C9H7Cl2N5

DETAILS

DrugBank - DB00555

• Drug Groups: approved; investigational
• 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]
• 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.
• Pharmacology: 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.
• 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
• Biotransformation: Hepatic
• Absorption: 98%
• Half Life: 25 +/- 10 hours (healthy individuals); 42.9 hours (chronic renal failure)
• Protein Binding: 55%
• Distribution: * 0.9 to 1.3 L/kg
• 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]
• References: Backonja M: Neuromodulating drugs for the symptomatic treatment of neuropathic pain. Curr Pain Headache Rep. 2004 Jun;8(3):212-6. [Pubmed] ; 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] ; Jensen TS: Anticonvulsants in neuropathic pain: rationale and clinical evidence. Eur J Pain. 2002;6 Suppl A:61-8. [Pubmed] ; Pappagallo M: Newer antiepileptic drugs: possible uses in the treatment of neuropathic pain and migraine. Clin Ther. 2003 Oct;25(10):2506-38. [Pubmed] ; 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: Wikipedia; RxList; Drugs.com

Sigma Aldrich - L3791

Biochem/physiol Actions
Anticonvulsant.
Packaging
10, 50 mg in glass bottle
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. L3791.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - L173250

An anticonvulsant. Inhibits glutamate release, possible through inhibition of Sodium, Potassium and Calcium currents. Used in treatment of bipolar depression.

REFERENCES

• Backonja M: Neuromodulating drugs for the symptomatic treatment of neuropathic pain. Curr Pain Headache Rep. 2004 Jun;8(3):212-6. Pubmed
• 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
• Jensen TS: Anticonvulsants in neuropathic pain: rationale and clinical evidence. Eur J Pain. 2002;6 Suppl A:61-8. Pubmed
• Pappagallo M: Newer antiepileptic drugs: possible uses in the treatment of neuropathic pain and migraine. Clin Ther. 2003 Oct;25(10):2506-38. Pubmed
• 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
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• Grunze, et al.: Neuropsychobiology, 38, 131 (1986)
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