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=NC(N)=C(N=N1)C2=C(Cl)C(Cl)=CC=C2

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 8228

Conditions

Condition	Modality	Targets	Highest Phase	Product
Epilepsy 122 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020241s045s051lbl.pdf	Primary		Approved 8360	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 7.8848642E11
Bipolar disorder 34 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020241s045s051lbl.pdf	Primary		Approved 8360	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 7.8848642E11

C_max

Value	Dose	Analyte	Population
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
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: age: sex: food status: Fed
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: age: sex: food status: Fasted

AUC

Value	Dose	Analyte	Population
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
113029.409999999 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: age: sex: food status: Fed
120080.26 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: age: sex: 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: age: sex: food status: Fed
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: age: sex: food status: Fasted

T_1/2

Value	Dose	Co-administered	Analyte	Population
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 1709 inhibitor 1579	substrate 1010 inhibitor 1752	substrate 1193 inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT2 638 CYP2B6 799 CYP1A2 1509 CYP2A6 704 CYP2C19 1463 CYP2E1 876 P-gp 1437 BSEP 401 OATP1B1 781 OATP1B3 700 OATP2B1 122 Nav1.5 95 Nav1.7 36 Cav1.2 45 Kv4.3 16	UGT 187 UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT1A9 380 UGT1A10 290 UGT2B4 249 UGT2B7 389 UGT2B15 203 UGT2B17 213 CYP1A2 1032 CYP2A6 523 CYP2B6 660 CYP2C8 688 CYP2C19 985 P-gp 1527 OCT1 322 OATP1A2 61 OATP1B3 347 OATP2B1 103 OCT3 79 OCT2 348 BCRP 555 MRP1 106 MRP2 201 MRP5 40	UGT 29

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1673	inhibitor 3240 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2A6 736	inhibitor 3240 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2C19 1537	inhibitor 3240 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2C9 1803	inhibitor 3240 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2D6 1875	inhibitor 3240 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 964	inhibitor 3240 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP3A4 1909	inhibitor 3240 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNzQxIn19	no [IC50 >10 uM]
BSEP 402	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
CYP2B6 985	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/17101742/	no
Kv4.3 16	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/25087753/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxOTY0IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no
OATP1B1 796	inhibitor 3240 Sources: https://pubs.acs.org/doi/10.1021/jm300212s	weak
OATP1B3 709	inhibitor 3240 Sources: https://pubs.acs.org/doi/10.1021/jm300212s	weak
OATP2B1 125	inhibitor 3240 Sources: https://pubs.acs.org/doi/10.1021/jm300212s	weak
UGT 58	inducer 1542 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 639	inhibitor 3240 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 36	inhibitor 3240 Sources: https://pubs.acs.org/doi/10.1021/jm801180p	yes
P-gp 1626	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12954800/, https://go.drugbank.com/drugs/DB00555	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT1A4 347	substrate 3326 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 422	substrate 3326 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 1032	substrate 3326 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 523	substrate 3326 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 660	substrate 3326 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 985	substrate 3326 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 688	substrate 3326 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 1010	substrate 3326 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 1193	substrate 3326 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 1709	substrate 3326 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 106	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/20080116/	no
MRP2 201	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/20080116/	no
MRP5 40	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/20080116/	no
OATP1A2 61	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	no
OCT2 348	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	no
OCT3 79	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	no
UGT1A1 418	substrate 3326 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 290	substrate 3326 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 307	substrate 3326 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 236	substrate 3326 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 283	substrate 3326 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 380	substrate 3326 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 203	substrate 3326 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 213	substrate 3326 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 249	substrate 3326 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 389	substrate 3326 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 555	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/25645391/	yes
OATP1B3 347	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	yes
OATP2B1 103	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	yes
OCT1 322	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/27317943/, https://go.drugbank.com/drugs/DB00555	yes
P-gp 1527	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/18824002/, https://go.drugbank.com/drugs/DB00555	yes
UGT 187	substrate 3326 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 49	inhibitor 1613 Sources: https://pubmed.ncbi.nlm.nih.gov/25087753/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxOTQwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D
Nav1.5 98	inhibitor 1613 Sources: https://pubs.acs.org/doi/10.1021/jm801180p
hERG 1632	inhibitor 1613 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
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
eMolecules	578746	https://www.emolecules.com/cgi-bin/more?vid=578746

PubMed

Title	Date	PubMed



Adding lamotrigine to valproate: incidence of rash and other adverse effects. Postmarketing Antiepileptic Drug Survey (PADS) Group.	1999 Aug	10448828
Lamotrigine as prophylaxis against steroid-induced mania.	1999 Oct	10549692
Acute hepatitis after lamotrigine administration.	2000 Sep	11052335
Adverse effects of antiepileptic drugs on bone structure: epidemiology, mechanisms and therapeutic implications.	2001	11524035
Effects of antiepileptic drugs on cognition.	2001	11422358
Incompleteness of lamotrigine data.	2001	11235819
Lamotrigine therapy for autistic disorder: a randomized, double-blind, placebo-controlled trial.	2001 Apr	11450816
Case reports.	2001 Apr	11437624
Effect of divalproex-lamotrigine combination therapy in frontal lobe seizures.	2001 Aug	11493167
A comparison of monotherapy with lamotrigine or carbamazepine in patients with newly diagnosed partial epilepsy.	2001 Aug	11463516
Adverse event monitoring in lamotrigine patients: a pharmacoepidemiologic study in the United Kingdom.	2001 Feb	11240596
The effect of lamotrigine on epileptiform discharges in young patients with drug-resistant epilepsy.	2001 Feb	11240595
Evaluating the tolerability of the newer mood stabilizers.	2001 Jan	11206668
Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V).	2001 Jan	11137386
Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy.	2001 Jan 23	11160951
Seizures, hormones and sexuality.	2001 Jul	11488644
The role of new antiepileptic drugs.	2001 Jul	11474769
Antiepileptic drug utilization: a Danish prescription database analysis.	2001 Jul	11442436
Lamotrigine in two cases of Rett syndrome.	2001 Jul	11377003
Teratogenic effects of lamotrigine on rat fetal brain: a morphometric study.	2001 Jun	11460180
Oxcarbazepine in focal epilepsy and hepatic porphyria: a case report.	2001 Jun	11422339
Preclinical evaluation of CHF3381 as a novel antiepileptic agent.	2001 Jun	11378157
Neurophysiological evaluation of vigilance in epileptic patients on monotherapy with lamotrigine.	2001 Jun	11377260
Single-dose pharmacokinetics of lamotrigine in children: influence of age and antiepileptic comedication.	2001 Jun	11360028
[SUNCT syndrome sensitive to lamotrigine].	2001 Jun 30	11484404
Absence epilepsy with fast rhythmic discharges during sleep: an intermediary form of generalized epilepsy?	2001 Mar	11442152
On the association between valproate and polycystic ovary syndrome.	2001 Mar	11442143
New generation anti-epileptics for facial pain and headache.	2001 Mar	11379275
Influence of retigabine on the anticonvulsant activity of some antiepileptic drugs against audiogenic seizures in DBA/2 mice.	2001 Mar	11284448
Anticonvulsant lamotrigine administered on reperfusion fails to improve experimental stroke outcomes.	2001 Mar	11239202
Influence of cirrhosis on lamotrigine pharmacokinetics.	2001 May	11421997
Lamotrigine: a review of clinical studies in bipolar disorders.	2001 May	11387788
Modulation of K+-evoked [3H]-noradrenaline release from rat and human brain slices by gabapentin: involvement of KATP channels.	2001 May	11383714
Mechanisms influencing stimulus-response properties of the human corticospinal system.	2001 May	11336911
A comparison of the effects of lamotrigine on neuroma-induced action potential firing and normal behaviour in rat: implications for establishing a pre-clinical 'therapeutic index'.	2001 May 18	11335043
Exacerbation of juvenile myoclonic epilepsy with lamotrigine.	2001 May 22	11376212
Differential cognitive and behavioral effects of carbamazepine and lamotrigine.	2001 May 8	11342682
Pharmacologic management of epilepsy in the elderly.	2001 May-Jun	11372907

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 `Wed Jul 05 22:46:45 UTC 2023` Edited by `admin` on `Wed Jul 05 22:46:45 UTC 2023`
Record UNII	U3H27498KS
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LAMOTRIGINE

Official Name

English

LAMOTRIGINE [HSDB]

Common Name

English

LAMICTAL

Brand 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