LAMOTRIGINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H7Cl2N5
Molecular Weight	256.091
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NN=C(C(N)=N1)C2=CC=CC(Cl)=C2Cl

InChI

InChIKey=PYZRQGJRPPTADH-UHFFFAOYSA-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)

HIDE SMILES / InChI

Molecular Formula	C9H7Cl2N5
Molecular Weight	256.091
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020241s045s051lbl.pdf

Lamotrigine (marketed as Lamictal) is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. The precise mechanism(s) by which lamotrigine exerts its anticonvulsant action are unknown. In animal models designed to detect anticonvulsant activity, lamotrigine was effective in preventing seizure spread in the maximum electroshock (MES) and pentylenetetrazol (scMet) tests, and prevented seizures in the visually and electrically evoked after-discharge (EEAD) tests for antiepileptic activity. Lamotrigine also displayed inhibitory properties in the kindling model in rats both during kindling development and in the fully kindled state. The relevance of these models to human epilepsy, however, is not known. 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, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate). Effect of Lamotrigine on N-Methyl d-Aspartate-Receptor Mediated Activity Lamotrigine did not inhibit N-methyl d-aspartate (NMDA)-induced depolarizations in rat cortical slices or NMDA-induced cyclic GMP formation in immature rat cerebellum, nor did lamotrigine displace compounds that are either competitive or noncompetitive ligands at this glutamate receptor complex (CNQX, CGS, TCHP). The IC50 for lamotrigine effects on NMDA-induced currents (in the presence of 3 uM of glycine) in cultured hippocampal neurons exceeded 100 uM. The mechanisms by which lamotrigine exerts its therapeutic action in bipolar disorder have not been established. The mechanisms that underpin the passage of lamotrigine at the blood-brain barrier to its site of action in the brain is poorly understood.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium channel alpha subunit 72 Target ID: CHEMBL2331043 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020241s045s051lbl.pdf	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Epilepsy 121 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020241s045s051lbl.pdf	Primary		Approved 8583	LAMICTAL Approved Use INDICATIONS & USAGE Lamotrigine is indicated for: Epilepsy—adjunctive therapy in patients aged 2 years and older: · partial-onset seizures. · primary generalized tonic-clonic seizures. · generalized seizures of Lennox-Gastaut syndrome. (1.1) Epilepsy—monotherapy in patients aged 16 years and older: Conversion to monotherapy in patients with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single AED. (1.1) Bipolar disorder: Maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in patients treated for acute mood episodes with standard therapy. (1.2) Limitations of Use: Treatment of acute manic or mixed episodes is not recommended. Effectiveness of lamotrigine in the acute treatment of mood episodes has not been established. 1.1 Epilepsy Adjunctive Therapy Lamotrigine is indicated as adjunctive therapy for the following seizure types in patients aged 2 years and older: · partial-onset seizures. · primary generalized tonic-clonic (PGTC) seizures. · generalized seizures of Lennox-Gastaut syndrome. Monotherapy Lamotrigine is indicated for conversion to monotherapy in adults (aged 16 years and older) with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED). Safety and effectiveness of lamotrigine have not been established (1) as initial monotherapy; (2) for conversion to monotherapy from AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate; or (3) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs. 1.2 Bipolar Disorder Lamotrigine is indicated for the maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in adults in patients treated for acute mood episodes with standard therapy [see Clinical Studies (14.1) Launch Date 1994
Bipolar disorder 34 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020241s045s051lbl.pdf	Primary		Approved 8583	LAMICTAL Approved Use INDICATIONS & USAGE Lamotrigine is indicated for: Epilepsy—adjunctive therapy in patients aged 2 years and older: · partial-onset seizures. · primary generalized tonic-clonic seizures. · generalized seizures of Lennox-Gastaut syndrome. (1.1) Epilepsy—monotherapy in patients aged 16 years and older: Conversion to monotherapy in patients with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single AED. (1.1) Bipolar disorder: Maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in patients treated for acute mood episodes with standard therapy. (1.2) Limitations of Use: Treatment of acute manic or mixed episodes is not recommended. Effectiveness of lamotrigine in the acute treatment of mood episodes has not been established. 1.1 Epilepsy Adjunctive Therapy Lamotrigine is indicated as adjunctive therapy for the following seizure types in patients aged 2 years and older: · partial-onset seizures. · primary generalized tonic-clonic (PGTC) seizures. · generalized seizures of Lennox-Gastaut syndrome. Monotherapy Lamotrigine is indicated for conversion to monotherapy in adults (aged 16 years and older) with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED). Safety and effectiveness of lamotrigine have not been established (1) as initial monotherapy; (2) for conversion to monotherapy from AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or valproate; or (3) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs. 1.2 Bipolar Disorder Lamotrigine is indicated for the maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in adults in patients treated for acute mood episodes with standard therapy [see Clinical Studies (14.1) Launch Date 1994

C_max

Value	Dose	Analyte	Population
4479 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16052246/	200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LAMOTRIGINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2912.04 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00834561	200 mg single, oral dose: 200 mg route of administration: oral experiment type: SINGLE co-administered:	LAMOTRIGINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: Fasted
2518 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00835263	200 mg single, oral dose: 200 mg route of administration: oral experiment type: SINGLE co-administered:	LAMOTRIGINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: Fed
4900 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20047572	150 mg 1 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LAMOTRIGINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
69754 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16052246/	200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LAMOTRIGINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
139995.13 ng × h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00834561	200 mg single, oral dose: 200 mg route of administration: oral experiment type: SINGLE co-administered:	LAMOTRIGINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: Fasted
131594.33 ng × h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00835263	200 mg single, oral dose: 200 mg route of administration: oral experiment type: SINGLE co-administered:	LAMOTRIGINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: Fed
73723 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20047572	150 mg 1 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LAMOTRIGINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
25 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16052246/	200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LAMOTRIGINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
22.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20047572	150 mg 1 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LAMOTRIGINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
45% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022251,020764s029,020241s036lbl.pdf			LAMOTRIGINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	substrate 1193 inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT2 779 CYP2B6 926 CYP1A2 2153 CYP2A6 879 CYP2C19 2057 CYP2E1 1060 P-gp 1741 BSEP 550 OATP1B1 1079 OATP1B3 961 OATP2B1 157 Nav1.5 116 Nav1.7 32 Cav1.2 58 Kv4.3 16	UGT 219 UGT1A1 479 UGT1A3 470 UGT1A4 399 UGT1A6 343 UGT1A7 249 UGT1A8 323 UGT1A9 423 UGT1A10 331 UGT2B4 278 UGT2B7 456 UGT2B15 236 UGT2B17 237 CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2C19 1119 P-gp 2052 OCT1 393 OATP1A2 67 OATP1B3 435 OATP2B1 122 OCT3 92 OCT2 434 BCRP 697 MRP1 113 MRP2 252 MRP5 41	UGT 32

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020241s058,020764s051,022251s022lbl.pdf#page=52, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNzQxIn19 Page: 52.0	no [IC50 >10 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNzQxIn19	no [IC50 >10 uM]
BSEP 554	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17101742/	no
Kv4.3 16	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/25087753/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxOTY0IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no
OATP1B1 1095	inhibitor 4027 Sources: https://pubs.acs.org/doi/10.1021/jm300212s	weak
OATP1B3 970	inhibitor 4027 Sources: https://pubs.acs.org/doi/10.1021/jm300212s	weak
OATP2B1 162	inhibitor 4027 Sources: https://pubs.acs.org/doi/10.1021/jm300212s	weak
UGT 70	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/9606477/, https://pubmed.ncbi.nlm.nih.gov/8823232/, https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=084057841	weak	yes (co-administration study) Comment: Coadministration of Lamotrigine decreased Valproate steady-state concentration by 25%. Sources: https://pubmed.ncbi.nlm.nih.gov/9606477/, https://pubmed.ncbi.nlm.nih.gov/8823232/, https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=084057841
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020241s058,020764s051,022251s022lbl.pdf#page=35 Page: 35-36, 52	yes [IC50 53.8 uM]
Nav1.7 32	inhibitor 4027 Sources: https://pubs.acs.org/doi/10.1021/jm801180p	yes
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12954800/, https://go.drugbank.com/drugs/DB00555	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT1A4 399	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, 39-40, (PMDA_K100) 50	major	yes (co-administration study) Comment: Coadministration of Valproic acid (UGT inducer) decreased Lamotrigine CL/F by about 50%. Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, 39-40, (PMDA_K100) 50
UGT1A3 470	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, 39-40, (PMDA_K100) 50	minor	yes (co-administration study) Comment: Coadministration of Valproic acid (UGT inducer) decreased Lamotrigine CL/F by about 50%. Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, 39-40, (PMDA_K100) 50
CYP1A2 1197	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50-51	no [IC50 >100 uM]
CYP2A6 626	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50-51	no [IC50 >100 uM]
CYP2B6 776	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50-51	no [IC50 >100 uM]
CYP2C19 1119	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50-51	no [IC50 >100 uM]
CYP2C8 810	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50-51	no [IC50 >100 uM]
CYP2C9 1193	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50-51	no [IC50 >100 uM]
CYP2D6 1388	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50-51	no [IC50 >100 uM]
CYP3A4 1946	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50-51	no [IC50 >100 uM]
MRP1 113	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/20080116/	no
MRP2 252	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/20080116/	no
MRP5 41	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/20080116/	no
OATP1A2 67	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	no
OCT2 434	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	no
OCT3 92	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	no
UGT1A1 479	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50	no
UGT1A10 331	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50	no
UGT1A6 343	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50	no
UGT1A7 249	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50	no
UGT1A8 323	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50	no
UGT1A9 423	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50	no
UGT2B15 236	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50	no
UGT2B17 237	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50	no
UGT2B4 278	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50	no
UGT2B7 456	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362000_A100_1.pdf#PAGE=31, https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_K100_1.pdf#page=50 Page: (PMDA) 31, (PMDA_K100) 50	no
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/25645391/	yes
OATP1B3 435	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	yes
OATP2B1 122	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	yes
OCT1 393	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27317943/, https://go.drugbank.com/drugs/DB00555	yes
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18824002/, https://go.drugbank.com/drugs/DB00555	yes
UGT 219	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020241s058,020764s051,022251s022lbl.pdf#page=34 Page: 34.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 63	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/25087753/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxOTQwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D
Nav1.5 119	inhibitor 2237 Sources: https://pubs.acs.org/doi/10.1021/jm801180p
hERG 2263	inhibitor 2237 Sources: https://www.pmda.go.jp/drugs/2008/P200800041/34027800_22000AMX02362_H100_1.pdf#page=34 Page: (PMDA_H100) 34

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6367	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6367
ChemicalBook	CB4166704	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4166704
eMolecules	578746	https://www.emolecules.com/cgi-bin/more?vid=578746
MolPort	MolPort-003-666-744	https://www.molport.com/shop/molecule-link/MolPort-003-666-744
Selleck Chemicals	lamotrigine	http://www.selleckchem.com/products/lamotrigine.html
ZINC	ZINC000000013156	http://zinc15.docking.org/substances/ZINC000000013156

PubMed

Title	Date	PubMed
Effect of lamotrigine treatment on status epilepticus-induced neuronal damage and memory impairment in rat.	2001-09	11518623
Spectrofluorimetric determination of vigabatrin and gabapentin in dosage forms and spiked plasma samples through derivatization with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole.	2001-08-15	11501899
Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study.	2001-08-14	11502921
Toxicologic causes of giggling.	2001-08	11512553
Newer antiepileptic drugs: advantages and disadvantages.	2001-08	11504596
Effect of divalproex-lamotrigine combination therapy in frontal lobe seizures.	2001-08	11493167
A comparison of monotherapy with lamotrigine or carbamazepine in patients with newly diagnosed partial epilepsy.	2001-08	11463516
Effect of gabapentin and lamotrigine on mechanical allodynia-like behaviour in a rat model of trigeminal neuropathic pain.	2001-08	11427326
Therapeutic drug monitoring of antiepileptics by capillary electrophoresis. Characterization of assays via analysis of quality control sera containing 14 analytes.	2001-07-27	11521893
Lamotrigine inhibition of glutamate release from isolated cerebrocortical nerve terminals (synaptosomes) by suppression of voltage-activated calcium channel activity.	2001-07-20	11447345
[Hypersensitivity to lamotrigine].	2001-07-19	11459532
Advances in the treatment of epilepsy.	2001-07-01	11456438
Lamotrigine therapy of epilepsy in tuberous sclerosis.	2001-07	11488895
Seizures, hormones and sexuality.	2001-07	11488644
The role of new antiepileptic drugs.	2001-07	11474769
Antiepileptic drug utilization: a Danish prescription database analysis.	2001-07	11442436
Neuroprotective effects of lamotrigine and remacemide on excitotoxicity induced by glutamate agonists in isolated chick retina.	2001-07	11421593
Normal growth during lamotrigine monotherapy in pediatric epilepsy patients -- a prospective evaluation of 103 children and adolescents.	2001-07	11395290
[SUNCT syndrome sensitive to lamotrigine].	2001-06-30	11484404
[Juvenile myoclonic epilepsy].	2001-06-26	11424054
[A casuistic report on Lamotrigine].	2001-06-20	11488193
Teratogenic effects of lamotrigine on rat fetal brain: a morphometric study.	2001-06	11460180
The Stanley Foundation Bipolar Network. 2. Preliminary summary of demographics, course of illness and response to novel treatments.	2001-06	11450180
Oxcarbazepine in focal epilepsy and hepatic porphyria: a case report.	2001-06	11422339
Extensive fixed drug eruption due to lamotrigine.	2001-06	11422075
Preclinical evaluation of CHF3381 as a novel antiepileptic agent.	2001-06	11378157
[Lamotrigine in the treatment of mental disorders].	2001-05-10	11449770
Lamotrigine analysis in blood and brain by high-performance liquid chromatography.	2001-05-05	11393695
[Optimal use of lamotrigine in clinical practice: results of an open multicenter trial in refractory epilepsy].	2001-05	11438772
Influence of cirrhosis on lamotrigine pharmacokinetics.	2001-05	11421997
Lamotrigine: a review of clinical studies in bipolar disorders.	2001-05	11387788
Modulation of K+-evoked [3H]-noradrenaline release from rat and human brain slices by gabapentin: involvement of KATP channels.	2001-05	11383714
Lamotrigine therapy for autistic disorder: a randomized, double-blind, placebo-controlled trial.	2001-04	11450816
Case reports.	2001-04	11437624
Epilepsy and the ovary (cutting out the hysteria).	2001-04	11437623
When treating patients with schizophrenia, what clinical points should be considered if lamotrigine is chosen to augment clozapine?	2001-03	11496920
Absence epilepsy with fast rhythmic discharges during sleep: an intermediary form of generalized epilepsy?	2001-03	11442152
On the association between valproate and polycystic ovary syndrome.	2001-03	11442143
A randomized open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy.	2001-03	11407953
New generation anti-epileptics for facial pain and headache.	2001-03	11379275
Adverse effects of antiepileptic drugs on bone structure: epidemiology, mechanisms and therapeutic implications.	2001	11524035
The management of refractory idiopathic epilepsies.	2001	11520320
Management strategies for refractory localization-related seizures.	2001	11520319
Epileptic encephalopathy.	2001	11520318
Bipolar rapid cycling: focus on depression as its hallmark.	2001	11469674
Introduction: the role of anticonvulsants as mood stabilizers.	2001	11469673
Cognitive side effects of anticonvulsants.	2001	11469672
Behavioural effects of the new anticonvulsants.	2001	11444724
Effects of antiepileptic drugs on cognition.	2001	11422358
Treatment of typical absence seizures and related epileptic syndromes.	2001	11393330

Patents

Sample Use Guides

In Vivo Use Guide

Epilepsy—Conversion From Adjunctive Therapy to Monotherapy: The recommended maintenance dose of LAMICTAL (lamotrigine) as monotherapy is 500 mg/day given in 2 divided doses.

Route of Administration: Oral

In Vitro Use Guide

In vitro, lamotrigine inhibited rat brain A-type of monoamine oxidase (MAO) activities with Ki values (MAO-A, 15 uM; MAO-B, 18 uM) potentially within the therapeutic range for this drug. The effects of lamotrigine on the MAO-A activities of rat brain and human liver preparations were almost identical suggesting minimal species or tissue variation

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:51:50 GMT 2025` Edited by `admin` on `Mon Mar 31 17:51:50 GMT 2025`
Record UNII	U3H27498KS
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LAMICTAL

Preferred Name

English

LAMOTRIGINE

Official Name

English

LAMOTRIGINE [HSDB]

Common Name

English

LAMOTRIGINE [JAN]

Common Name

English

LAMOTRIGINE [MART.]

Common Name

English

lamotrigine [INN]

Common Name

English

1,2,4-TRIAZINE-3,5-DIAMINE, 6-(2,3-DICHLOROPHENYL)

Common Name

English

LAMOTRIGINE [EP MONOGRAPH]

Common Name

English

LAMOTRIGINE [MI]

Common Name

English

BW-430C

Code

English

Lamotrigine [WHO-DD]

Common Name

English

LAMOTRIGINE [ORANGE BOOK]

Common Name

English

LAMOTRIGINE [EP IMPURITY]

Common Name

English

LAMOTRIGINE [USP-RS]

Common Name

English

LAMOTRIGINE [USP MONOGRAPH]

Common Name

English

LAMOTRIGINE [USAN]

Common Name

English

LAMOTRIGINE [USP IMPURITY]

Common Name

English

3,5-Diamino-6-(2,3-dichlorophenyl)-as-triazine

Common Name

English

BW 430C

Code

English

NSC-759171

Code

English

Classification Tree Code System Code

NDF-RT

N0000175753