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

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 76 Target ID: CHEMBL2331043 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020241s045s051lbl.pdf	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Epilepsy 121 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020241s045s051lbl.pdf	Primary		Approved 8429	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 8429	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 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT2 647 CYP2B6 810 CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882 P-gp 1461 BSEP 402 OATP1B1 788 OATP1B3 706 OATP2B1 123 Nav1.5 97 Nav1.7 36 Cav1.2 45 Kv4.3 16	UGT 192 UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT1A9 380 UGT1A10 291 UGT2B4 249 UGT2B7 389 UGT2B15 203 UGT2B17 213 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 P-gp 1537 OCT1 327 OATP1A2 62 OATP1B3 350 OATP2B1 104 OCT3 80 OCT2 355 BCRP 561 MRP1 107 MRP2 205 MRP5 40	UGT 29

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2D6 1891	inhibitor 3277 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 970	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no [IC50 >10 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNzQxIn19	no [IC50 >10 uM]
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17101742/	no
Kv4.3 16	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25087753/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxOTY0IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D	no
OATP1B1 803	inhibitor 3277 Sources: https://pubs.acs.org/doi/10.1021/jm300212s	weak
OATP1B3 715	inhibitor 3277 Sources: https://pubs.acs.org/doi/10.1021/jm300212s	weak
OATP2B1 126	inhibitor 3277 Sources: https://pubs.acs.org/doi/10.1021/jm300212s	weak
UGT 59	inducer 1573 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 648	inhibitor 3277 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 3277 Sources: https://pubs.acs.org/doi/10.1021/jm801180p	yes
P-gp 1650	inhibitor 3277 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 3367 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 3367 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 1054	substrate 3367 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 543	substrate 3367 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 664	substrate 3367 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 991	substrate 3367 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 693	substrate 3367 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 1037	substrate 3367 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 1217	substrate 3367 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 1737	substrate 3367 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 107	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20080116/	no
MRP2 205	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20080116/	no
MRP5 40	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20080116/	no
OATP1A2 62	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	no
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	no
OCT3 80	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	no
UGT1A1 418	substrate 3367 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 291	substrate 3367 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 3367 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 3367 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 3367 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 3367 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 3367 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 3367 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 3367 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 3367 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 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25645391/	yes
OATP1B3 350	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	yes
OATP2B1 104	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22227272/	yes
OCT1 327	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27317943/, https://go.drugbank.com/drugs/DB00555	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18824002/, https://go.drugbank.com/drugs/DB00555	yes
UGT 192	substrate 3367 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 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/25087753/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxOTQwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDc0MSJ9fQ%3D%3D
Nav1.5 100	inhibitor 1626 Sources: https://pubs.acs.org/doi/10.1021/jm801180p
hERG 1647	inhibitor 1626 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
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
Lamotrigine therapy for autistic disorder: a randomized, double-blind, placebo-controlled trial.	2001 Apr	11450816
Case reports.	2001 Apr	11437624
Epilepsy and the ovary (cutting out the hysteria).	2001 Apr	11437623
Toxicologic causes of giggling.	2001 Aug	11512553
Newer antiepileptic drugs: advantages and disadvantages.	2001 Aug	11504596
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
Effect of gabapentin and lamotrigine on mechanical allodynia-like behaviour in a rat model of trigeminal neuropathic pain.	2001 Aug	11427326
Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study.	2001 Aug 14	11502921
Lamotrigine therapy of epilepsy in tuberous sclerosis.	2001 Jul	11488895
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
Neuroprotective effects of lamotrigine and remacemide on excitotoxicity induced by glutamate agonists in isolated chick retina.	2001 Jul	11421593
Normal growth during lamotrigine monotherapy in pediatric epilepsy patients -- a prospective evaluation of 103 children and adolescents.	2001 Jul	11395290
Advances in the treatment of epilepsy.	2001 Jul 1	11456438
Lamotrigine inhibition of glutamate release from isolated cerebrocortical nerve terminals (synaptosomes) by suppression of voltage-activated calcium channel activity.	2001 Jul 20	11447345
Therapeutic drug monitoring of antiepileptics by capillary electrophoresis. Characterization of assays via analysis of quality control sera containing 14 analytes.	2001 Jul 27	11521893
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 Jul-Aug	11501899
[Hypersensitivity to lamotrigine].	2001 Jul-Aug	11459532
Teratogenic effects of lamotrigine on rat fetal brain: a morphometric study.	2001 Jun	11460180
The Stanley Foundation Bipolar Network. 2. Preliminary summary of demographics, course of illness and response to novel treatments.	2001 Jun	11450180
Oxcarbazepine in focal epilepsy and hepatic porphyria: a case report.	2001 Jun	11422339
Extensive fixed drug eruption due to lamotrigine.	2001 Jun	11422075
Preclinical evaluation of CHF3381 as a novel antiepileptic agent.	2001 Jun	11378157
[A casuistic report on Lamotrigine].	2001 Jun 20	11488193
[SUNCT syndrome sensitive to lamotrigine].	2001 Jun 30	11484404
When treating patients with schizophrenia, what clinical points should be considered if lamotrigine is chosen to augment clozapine?	2001 Mar	11496920
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
A randomized open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy.	2001 Mar	11407953
New generation anti-epileptics for facial pain and headache.	2001 Mar	11379275
[Optimal use of lamotrigine in clinical practice: results of an open multicenter trial in refractory epilepsy].	2001 May	11438772
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
[Lamotrigine in the treatment of mental disorders].	2001 May 10	11449770
[Juvenile myoclonic epilepsy].	2001 May 16-31	11424054
Lamotrigine analysis in blood and brain by high-performance liquid chromatography.	2001 May 5	11393695
Effect of lamotrigine treatment on status epilepticus-induced neuronal damage and memory impairment in rat.	2001 Sep	11518623

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

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