Lamotrigine

Summary

Lamotrigine (CHEMBL741) is an approved small-molecule anticonvulsant (ATC N03AX09) targeting SCN2A; indicated across 32 conditions including epilepsy and visual epilepsy.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N03AX09
• Targets: 1 (SCN2A)
• Indications: 32 conditions
• Clinical trials: 159
• Chemistry: 256.09 Da · C9H7Cl2N5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL741
Name	Lamotrigine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3878
ChEBI	CHEBI:6367
ATC	N03AX09
Molecular formula	C9H7Cl2N5
Molecular weight	256.09
InChIKey	PYZRQGJRPPTADH-UHFFFAOYSA-N

SMILES: C1=CC(=C(C(=C1)Cl)Cl)C2=C(N=C(N=N2)N)N

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

ChEBI definition: A member of the class of 1,2,4-triazines in which the triazene skeleton is substituted by amino groups at positions 3 and 5, and by a 2,3-dichlorophenyl group at position 6.

Pharmacological roles (ChEBI): anticonvulsant, antimanic drug, antidepressant, non-narcotic analgesic, calcium channel blocker, excitatory amino acid antagonist, EC 3.4.21.26 (prolyl oligopeptidase) inhibitor, geroprotector.

Other ChEBI roles (chemical / environmental): environmental contaminant, xenobiotic.

Also known as: BW 430C, BW-430C, Lamictal, Lamictal cd, Lamictal odt, Lamictal xr, Lamotrigina, Lamotrigine, NSC-759171, lamotrigine, SID11113342, SID26719658

Patent coverage: 7,364 distinct patent families (28,962 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 28,749 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
SCN2A	Nav1.2	Pore blocker	4.5	0.1%	Q99250

Broader ChEMBL bioactivity targets: 19 (assay-derived). Sample: RecQ-like DNA helicase BLM, Peripheral myelin protein 22, Dihydrofolate reductase, Amine oxidase [flavin-containing] A, Sodium channel protein type 5 subunit alpha, Sodium channel protein type 4 subunit alpha, Sodium channel alpha subunits; brain (Types I, II, III), Alpha-1A adrenergic receptor, cGMP-inhibited 3’,5’-cyclic phosphodiesterase 3A, Muscarinic acetylcholine receptor M1.

Bioactivity

ChEMBL activities: 5 potent at pChembl ≥ 5 of 27 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PDE3A	5.68	AC50	2100	nM	CHEMBL_ACT_25191180
P08482	5.6	Potency	2512	nM	CHEMBL_ACT_4857884
CYP2D6	5.2	Potency	6310	nM	CHEMBL_ACT_5006461
CYP2D6	5.2	AC50	6310	nM	CHEMBL_ACT_6050150
SCN2A	5	IC50	10000	nM	CHEMBL_ACT_2344169

Target pathways

Aggregated over 1 target gene(s): SCN2A.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
Developmental Biology	1	SCN2A
L1CAM interactions	1	SCN2A
Muscle contraction	1	SCN2A
Axon guidance	1	SCN2A
Interaction between L1 and Ankyrins	1	SCN2A
Cardiac conduction	1	SCN2A
Phase 0 - rapid depolarisation	1	SCN2A
Nervous system development	1	SCN2A
Sensory Perception	1	SCN2A
Sensory perception of taste	1	SCN2A
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	SCN2A

Dominant GO biological processes

GO term	Targets
sodium ion transport	1
nervous system development	1
memory	1
intrinsic apoptotic signaling pathway in response to osmotic stress	1
neuronal action potential	1
sodium ion transmembrane transport	1
myelination	1
neuron apoptotic process	1
cellular response to hypoxia	1
cardiac muscle cell action potential involved in contraction	1
action potential	1
regulation of heart rate	1
monoatomic ion transport	1
monoatomic ion transmembrane transport	1
regulation of membrane potential	1

Indications & clinical

Indications

32 indications (10 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
epilepsy	4	MONDO:0005027	EFO:0000474
visual epilepsy	4	MONDO:0001386	HP:0001250
focal epilepsy	4	MONDO:0005384	EFO:0004263
epilepsy with generalized tonic-clonic seizures	4	MONDO:0005754	HP:0002069
depressive disorder	4	MONDO:0002050	MONDO:0002050
bipolar disorder	4	MONDO:0004985	EFO:0009963
Lennox-Gastaut syndrome	4	MONDO:0016532	MONDO:0016532
mood disorder	3	MONDO:0005371	EFO:0004247
peripheral neuropathy	3	MONDO:0005244	EFO:0003100
anxiety	3	MONDO:0011918	EFO:0005230
dementia	3	MONDO:0001627	HP:0000726
obesity disorder	3	MONDO:0011122	EFO:0001073
eating disorder	3	MONDO:0005451	EFO:0005203
relapsing-remitting multiple sclerosis	2	MONDO:0005314	EFO:0003929
drug dependence	2	MONDO:0005303	EFO:0003890
cocaine dependence	2	MONDO:0005186	EFO:0002610
opiate dependence	2	MONDO:0005530	EFO:0005611
secondary progressive multiple sclerosis	2	MONDO:0000450	EFO:0008522
alcohol abuse	2	MONDO:0002046	MONDO:0007079
neurofibromatosis type 1	2	MONDO:0018975	MONDO:0018975
mental disorder	1	MONDO:0005084	EFO:0000677
HIV infectious disease	1	MONDO:0005109	EFO:0000764

10 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 159.

Phase distribution

Phase	Trials
PHASE4	38
PHASE1	36
PHASE3	34
Not specified	32
PHASE2	17
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05881928	PHASE4	NOT_YET_RECRUITING	Effect of Adding Lamotrigine to Sodium Valproate in Childhood Epilepsy: Clinicolabratory Study
NCT06184581	PHASE4	RECRUITING	Lithium Versus Lamotrigine in Bipolar Disorder, Type II
NCT00043901	PHASE4	COMPLETED	Treatment Of Primary Generalized Tonic-Clonic Seizures With An Investigational New Drug
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00067938	PHASE4	COMPLETED	Bipolar Study in Adults at Least 18 Years of Age
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00153244	PHASE4	COMPLETED	Study of Efficacy of Lamotrigine in Therapy of Bronchial Asthma
NCT00177567	PHASE4	COMPLETED	Treatment of Geriatric Bipolar Mood Disorders: A Pilot Study
NCT00181844	PHASE4	COMPLETED	Lamotrigine for the Treatment of Mania in Youth Ages 6-17 With Bipolar Disorder
NCT00183469	PHASE4	COMPLETED	Maintenance Treatment of Bipolar Depression
NCT00188643	PHASE4	COMPLETED	Venlafaxine Versus Lamotrigine in the Treatment of Bipolar I/II Depression
NCT00223262	PHASE4	COMPLETED	Clinical Trial of Lamotrigine to Reverse Cognitive Impairment in Chronic Corticosteroid-Treated Patients
NCT00223509	PHASE4	COMPLETED	Lamictal As Add on Treatment in Mixed States of Bipolar Disorder
NCT00277212	PHASE4	COMPLETED	A Phase IV Study of the Safety and Efficacy of Aripiprazole in Combination With Lamotrigine in the Long-Term Maintenance Treatment of Patients With Bipolar I Disorder With A Recent Manic or Mixed Episode
NCT00280293	PHASE4	COMPLETED	Lamotrigine add-on Therapy for Bipolar Disorder and Cocaine Dependency
NCT00360126	PHASE4	COMPLETED	An Open-Label Extension Study Of Lamotrigine In Subjects With Bipolar Disorder
NCT00419003	PHASE4	COMPLETED	Research Study for Major Depressive Disorder: Investigation of Glutamate Medications
NCT00438451	PHASE4	COMPLETED	Study on the Treatment of Elderly Patients With Older and Newer Antiepileptic Drugs
NCT00485771	PHASE4	COMPLETED	Olanzapine/Fluoxetine Combination Versus Comparator in the Treatment of Bipolar I Depression
NCT00634062	PHASE4	COMPLETED	Study of Lamotrigine Treatment of Affective Instability in Borderline Personality Disorder
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00855738	PHASE4	COMPLETED	A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00926835	PHASE4	TERMINATED	Effect of Antidepressants on the Treatment for Korean Major Depressive Disorder Patients
NCT01015586	PHASE4	COMPLETED	Treatment of Alcohol Dependence and Comorbid Bipolar Disorder
NCT01142310	PHASE4	COMPLETED	Reversing Corticosteroid Induced Memory Impairment
NCT01588457	PHASE4	COMPLETED	Sequential Multiple Assignment Treatment for Bipolar Disorder
NCT01733394	PHASE4	COMPLETED	Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy: Single-Dose 6-Period Replicate Design (EQUIGEN Single-Dose Study)
NCT01864551	PHASE4	COMPLETED	Olanzapine Compared to Lamotrigine in the Prevention of Depressive Episode in the Patients With Bipolar Disorder
NCT01995825	PHASE4	COMPLETED	Lamotrigine Bioequivalence
NCT02100644	PHASE4	COMPLETED	Valproate Dose Reduction and Its Clinical Evaluation by Introducing Lamotrigine in Japanese Women With Epilepsy - Single Arm, Multicenter, and Open-label Study
NCT02303106	PHASE4	COMPLETED	Interaction Between Paracetamol and Lamotrigine: A Clinical Interaction Study
NCT02389712	PHASE4	TERMINATED	16-week Comparative Effectiveness Trial of Lamotrigine vs. Fluoxetine for Bipolar Depression
NCT02989727	PHASE4	COMPLETED	Melancholic Symptoms in Bipolar Depression and Responsiveness to Lamotrigine
NCT03161509	PHASE4	TERMINATED	Pharmacokinetics of Paracetamol and Antiepileptic Drugs After Sleeve Gastrectomy
NCT04523935	PHASE4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05697614	PHASE4	UNKNOWN	The Benefit and Safety of Older Generation Anti-Epileptic Drugs (AEDs) in Drug-Resistant Epilepsy Children
NCT05748236	PHASE4	UNKNOWN	The Efficacy and Safety of Lamotrigine Versus Carbamazepine in Focal Epilepsy
NCT06929273	PHASE3	RECRUITING	A Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-3)
NCT00007670	PHASE3	COMPLETED	Does Gabapentin and Lamotriginel Have Significantly Fewer Side-effects While Providing Equal or Better Seizure Control Than the Current Drug Choice, Carbamazepine, for the Treatment of Seizures in the Elderly.

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (1) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of DPWG Guideline for lamotrigine and HLA-B	DPWG	HLA-B		yes

PharmGKB also curates 17 clinical and 144 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

134 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
AMIODARONE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
AMITRIPTYLINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
BROMPHENIRAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
CHLORPHENIRAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
CHLORPROMAZINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
COCAINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
CYPROHEPTADINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
DESIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
DIBUCAINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
DICYCLOMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
DILTIAZEM	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
DIPHENHYDRAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
DROPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
FELODIPINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
FLUPHENAZINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
HALOPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
LEVORPHANOL	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
LOPERAMIDE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
MEXILETINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
NIFEDIPINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
NISOLDIPINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
PHENOXYBENZAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
PHENTOLAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
PHENYTOIN	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
PIMOZIDE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
PRAMOXINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
PRAZOSIN	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
PRILOCAINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
PROMETHAZINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
PROPARACAINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
QUINIDINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
QUININE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
RESERPINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
TETRABENAZINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
TETRACAINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
THIORIDAZINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
TRIFLUOPERAZINE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
VERAPAMIL	ChEMBL + PubChem	Phase 4 (approved)	SCN2A
ARTICAINE	ChEMBL	Phase 4 (approved)	SCN2A
BENOXINATE	ChEMBL	Phase 4 (approved)	SCN2A
BEPRIDIL	ChEMBL	Phase 4 (approved)	SCN2A
BUPIVACAINE	ChEMBL	Phase 4 (approved)	SCN2A
CINNARIZINE	ChEMBL	Phase 4 (approved)	SCN2A
DIPHENIDOL	ChEMBL	Phase 4 (approved)	SCN2A
ETIDOCAINE	ChEMBL	Phase 4 (approved)	SCN2A
HEXYLCAINE	ChEMBL	Phase 4 (approved)	SCN2A
MIANSERIN	ChEMBL	Phase 4 (approved)	SCN2A
MIBEFRADIL	ChEMBL	Phase 4 (approved)	SCN2A
PHENIRAMINE	ChEMBL	Phase 4 (approved)	SCN2A
PRENYLAMINE	ChEMBL	Phase 4 (approved)	SCN2A
PROMAZINE	ChEMBL	Phase 4 (approved)	SCN2A
PROPOXYCAINE	ChEMBL	Phase 4 (approved)	SCN2A
QUINACRINE	ChEMBL	Phase 4 (approved)	SCN2A
RILUZOLE	ChEMBL	Phase 4 (approved)	SCN2A
SERTINDOLE	ChEMBL	Phase 4 (approved)	SCN2A
YOHIMBINE	ChEMBL + PubChem	Phase 3 (approved)	SCN2A
AJMALINE	ChEMBL	Phase 3	SCN2A
ELECLAZINE	ChEMBL	Phase 3	SCN2A
NITRENDIPINE	ChEMBL	Phase 3	SCN2A