Drug Information

Drug (ID: DG00639) and It's Reported Resistant Information

• Name: Lamotrigine
• Synonyms: Lamotrigine; 84057-84-1; 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine; Lamictal; Lamictal Cd; Lamictal XR; Lamotriginum [Latin]; Lamotrigina [Spanish]; Lamotriginum; BW 430C; Lamotrigina; Lamictal ODT; BW-430C; 3,5-Diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine; 1,2,4-Triazine-3,5-diamine, 6-(2,3-dichlorophenyl)-; BW430C; 3,5-Diamino-6-(2,3-dichlorophenyl)-as-triazine; C9H7Cl2N5; LTG;BW430C; UNII-U3H27498KS; MFCD00865333; CHEMBL741; MLS000069685; CHEBI:6367; U3H27498KS; NSC-759171; NCGC00015605-06; Labileno; Lamitor; SMR000058464; Lamotrigine-13C-d3; DSSTox_CID_3195; DSSTox_RID_76918; DSSTox_GSID_23195; Lamictal (TN); LTg; CAS-84057-84-1; SR-01000000187; EINECS 281-901-8; HSDB 7526; EUR-1048; Lamotrigine [USAN:USP:INN:BAN]; zine-3,5-diamine; Lamotrigine- Bio-X; GI 267119X; Opera_ID_12; Tocris-1611; hydroxymethyl progesterone; Lopac-L-3791; L 3791; Lopac0_000688; SCHEMBL35439; MLS000759486; MLS001077325; MLS001423991; BIDD:GT0794; Lamotrigine (JAN/USP/INN); Lamotrigine, >=98%, powder; GTPL2622; DTXSID2023195; ZINC13156; HMS2051C10; HMS2089M08; HMS2093P21; HMS2230L04; HMS3262I17; HMS3268G17; HMS3371O16; HMS3393C10; HMS3657A17; HMS3715H21; HMS3885M03; Pharmakon1600-01505610; AMY40805; BCP12156; HY-B0495; Lamotrigine 1.0 mg/ml in Methanol; Tox21_110179; Tox21_500688; BDBM50031299; NSC746307; NSC759171; s3024; STK628377; AKOS005561147; Tox21_110179_1; 6-(2,2,4-triazine-3,5-diyldiamine; CCG-100856; DB00555; KS-1074; LP00688; MCULE-7648410888; NC00106; NSC 746307; NSC 759171; NSC-746307; SDCCGSBI-0050666.P003; SMP2_000303; NCGC00015605-01; NCGC00015605-02; NCGC00015605-03; NCGC00015605-04; NCGC00015605-05; NCGC00015605-07; NCGC00015605-08; NCGC00015605-09; NCGC00015605-10; NCGC00015605-23; NCGC00015605-24; NCGC00022936-02; NCGC00022936-04; NCGC00022936-05; NCGC00261373-01; AC-10298; AC-32483; BL166799; K499; Lamotrigine 100 microg/mL in Acetonitrile; SBI-0050666.P002; 6-(2,3-Dichloro-phenyl)-[1,2,4]tria; DB-014839; B2249; EU-0100688; FT-0602546; FT-0670713; FT-0670714; L-205; L0241; SW197486-3; 57L841; A11873; D00354; J10032; W13018; AB00384359-16; AB00384359_17; AB00384359_18; A840709; Q410346; 3,5-diamino-(2,3-dichlorophenyl)-1,2,4-triazine; Q-201221; SR-01000000187-2; SR-01000000187-4; SR-01000000187-7; BRD-K93460210-071-01-6; SR-01000000187-10; 3,5-diamino-6-(2,3,-dichlorophenyl)-1,2,4-triazine; 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine.; F2173-0540; Z1550648755; 6-(2,3-Dichloro-phenyl)-[1,2,4]triazine-3,5-diamine; 6-[2,3-bis(chloranyl)phenyl]-1,2,4-triazine-3,5-diamine; Lamotrigine, British Pharmacopoeia (BP) Reference Standard; Lamotrigine, European Pharmacopoeia (EP) Reference Standard; 6-(2,3-Dichloro-phenyl)-[1,2,4]triazine-3,5-diamine(lamotrigine); GI 267119X; 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine; Lamotrigine, United States Pharmacopeia (USP) Reference Standard; Lamotrigine, Pharmaceutical Secondary Standard; Certified Reference Material; Lamotrigine for peak identification, European Pharmacopoeia (EP) Reference Standard; Lamotrigine for system suitability, European Pharmacopoeia (EP) Reference Standard; Lamotrigine solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material
• Indication:
  In total 2 Indication(s)
  Bipolar disorder [ICD-11: 6A60]; Approved; [1]
  Epilepsy [ICD-11: 8A60]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Epilepsy [ICD-11: 8A60]; [3]
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Genetic epileptic syndromes [ICD-11: 8A61]; [4]
• Target: Voltage-gated sodium channel alpha Nav1.9 (SCN11A); SCNBA_HUMAN; [1]
• Formula: C9H7Cl2N5
• IsoSMILES: C1=CC(=C(C(=C1)Cl)Cl)C2=C(N=C(N=N2)N)N
• 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
• PubChem CID: 3878
• ChEBI ID: CHEBI:6367
• TTD Drug ID: D03FLC
• VARIDT ID: DR00056
• INTEDE ID: DR0913
• DrugBank ID: DB00555

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-08: Nervous system diseases

Epilepsy [ICD-11: 8A60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [2]

• Resistant Disease: Epilepsy [ICD-11: 8A60.0]
• Molecule Alteration: Missense mutation; p.V2424G
• Experiment for Molecule Alteration: Genotyping assay; RT-PCR
• Experiment for Drug Resistance: High-performance liquid chromatography assay; Diode-array assay
• Mechanism Description: Polymorphism ABCG2 c.421C>A moderately reduces lamotrigine concentrations in adults with epilepsy.

Key Molecule: Glutathione synthetase (GSH) [3]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: Ellman assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Key Molecule: Quinone reductase 1 (NQO1) [3]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Nrf2 signaling pathway; Inhibition; hsa05208
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: ELISA assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Genetic epileptic syndromes [ICD-11: 8A61]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) [1]

• Sensitive Disease: Genetic generalized epilepsies [ICD-11: 8A61.0]
• Molecule Alteration: SNP; rs12402969 C+ Genotypes CC+CT
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genotyping assay
• Mechanism Description: By analyzing the association between KCNJ10 polymorphisms and anti-epileptic drug efficacy of GGEs we found the frequency of rs12402969 C allele and CC+CT genotypes were higher in GGEs drug responsive patients than that in drug resistant patients

References

• Ref 1: Common variants of KCNJ10 are associated with susceptibility and anti-epileptic drug resistance in Chinese genetic generalized epilepsies .PLoS One. 2015 Apr 13;10(4):e0124896. doi: 10.1371/journal.pone.0124896. eCollection 2015. 10.1371/journal.pone.0124896
• Ref 2: The Loss-of-Function ATP Binding Cassette Subfamily G Member 2 Polymorphism ABCG2 c.421C>A Reduces Lamotrigine Trough Concentrations in Adults with Epilepsy. Eur J Drug Metab Pharmacokinet. 2025 Jan;50(1):17-22.
• Ref 3: Attenuation of mitochondrial refractory epilepsy in rotenone corneal kindling model of drug resistance by idebenone: An approach to bypass mitochondrial complex I. Epilepsy Res. 2024 Nov;207:107458.
• Ref 4: Drug-Resistant Juvenile Myoclonic Epilepsy: Misdiagnosis of Progressive Myoclonus EpilepsyFront Neurol. 2019 Sep 10;10:946. doi: 10.3389/fneur.2019.00946. eCollection 2019.