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 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 1994
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 1994

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
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
[Lyell syndrome associated with lamotrigine].	2000 Dec 16-31	11205551
The management of refractory idiopathic epilepsies.	2001	11520320
Management strategies for refractory localization-related seizures.	2001	11520319
Introduction: the role of anticonvulsants as mood stabilizers.	2001	11469673
Effects of antiepileptic drugs on cognition.	2001	11422358
The long-term use of vigabatrin and lamotrigine in patients with severe childhood onset epilepsy.	2001	11277363
Lamotrigine therapy for autistic disorder: a randomized, double-blind, placebo-controlled trial.	2001 Apr	11450816
The combination of lamotrigine and mild hypothermia prevents ischemia-induced increase in hippocampal glutamate.	2001 Apr	11294451
Tonabersat (SB-220453) a novel benzopyran with anticonvulsant properties attenuates trigeminal nerve-induced neurovascular reflexes.	2001 Apr	11264249
[Sensory neuropathy in HIV infection: pathogenesis and therapy].	2001 Apr 14	11332255
Peri-marketing surveillance of lamotrigine in The Netherlands: doctors' and patients' viewpoints.	2001 Feb	11344584
Infantile spasms.	2001 Feb	11275456
The effect of lamotrigine on epileptiform discharges in young patients with drug-resistant epilepsy.	2001 Feb	11240595
The neuroprotective agent sipatrigine (BW619C89) potently inhibits the human tandem pore-domain K(+) channels TREK-1 and TRAAK.	2001 Feb 16	11172753
Electrophysiological and pharmacological properties of the human brain type IIA Na+ channel expressed in a stable mammalian cell line.	2001 Jan	11212204
Evaluating the tolerability of the newer mood stabilizers.	2001 Jan	11206668
Lamotrigine for central poststroke pain: a randomized controlled trial.	2001 Jan 23	11160953
Molecular determinants of voltage-dependent gating and binding of pore-blocking drugs in transmembrane segment IIIS6 of the Na(+) channel alpha subunit.	2001 Jan 5	11024055
[Glutaminergic hypothesis of schizophrenia: clinical research studies with ketamine].	2001 Jan-Feb	11294039
The role of new antiepileptic drugs.	2001 Jul	11474769
Antiepileptic drug utilization: a Danish prescription database analysis.	2001 Jul	11442436
Single-dose pharmacokinetics of lamotrigine in children: influence of age and antiepileptic comedication.	2001 Jun	11360028
Absence epilepsy with fast rhythmic discharges during sleep: an intermediary form of generalized epilepsy?	2001 Mar	11442152
Anticonvulsant lamotrigine administered on reperfusion fails to improve experimental stroke outcomes.	2001 Mar	11239202
[Optimal use of lamotrigine in clinical practice: results of an open multicenter trial in refractory epilepsy].	2001 May	11438772
Effects of extracellular pH on the interaction of sipatrigine and lamotrigine with high-voltage-activated (HVA) calcium channels in dissociated neurones of rat cortex.	2001 May	11369032
Mechanisms influencing stimulus-response properties of the human corticospinal system.	2001 May	11336911
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
Treatment-resistant bipolar disorder.	2001 Winter	11280956

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 `Fri Dec 15 15:15:28 GMT 2023` Edited by `admin` on `Fri Dec 15 15:15:28 GMT 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