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Details

Stereochemistry ACHIRAL
Molecular Formula C9H7Cl2N5
Molecular Weight 256.0916
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LAMOTRIGINE

SMILES

c1cc(c(c(c1)Cl)Cl)-c2c(N)[nH]c(=N)nn2

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
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

Curator's Comment:: The mechanisms that underpin the passage of lamotrigine at the blood-brain barrier to its site of action in the brain is poorly understood.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Primary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4900 ng/mL
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
73723 ng × h/mL
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
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
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
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
22.6 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
45%
LAMOTRIGINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >133 uM]
no
no
weak
weak
weak
weak
yes (co-administration study)
yes [IC50 53.8 uM]
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: Coadministration of Valproic acid (UGT inducer) decreased Lamotrigine CL/F by about 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%.
Page: (PMDA) 31, 39-40, (PMDA_K100) 50
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes
yes
yes
yes
yes
yes
Tox targets
PubMed

PubMed

TitleDatePubMed
Pramipexole treatment for cocaine cravings.
1999 Nov
[The use of lamotrigine in the psychosocial readaptation of patients with epilepsy].
2000 Jul 1-15
Improved sexual function in three men taking lamotrigine for epilepsy.
2000 Mar
Introduction: the role of anticonvulsants as mood stabilizers.
2001
The long-term use of vigabatrin and lamotrigine in patients with severe childhood onset epilepsy.
2001
Epilepsy and the ovary (cutting out the hysteria).
2001 Apr
The combination of lamotrigine and mild hypothermia prevents ischemia-induced increase in hippocampal glutamate.
2001 Apr
Toxicologic causes of giggling.
2001 Aug
Effect of divalproex-lamotrigine combination therapy in frontal lobe seizures.
2001 Aug
Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V).
2001 Jan
[SUNCT syndrome sensitive to lamotrigine].
2001 Jun 30
On the association between valproate and polycystic ovary syndrome.
2001 Mar
pH-stat strategy and hypothermia of 25 degrees C alone should protect the central nervous system consistently from 75 minutes of circulatory arrest.
2001 Mar
[Optimal use of lamotrigine in clinical practice: results of an open multicenter trial in refractory epilepsy].
2001 May
Modulation of K+-evoked [3H]-noradrenaline release from rat and human brain slices by gabapentin: involvement of KATP channels.
2001 May
[Juvenile myoclonic epilepsy].
2001 May 16-31
Effect of lamotrigine treatment on status epilepticus-induced neuronal damage and memory impairment in rat.
2001 Sep
Treatment-resistant bipolar disorder.
2001 Winter
Patents

Patents

Sample Use Guides

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, 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
EP   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
LAMOTRIGINE [HSDB]
Common Name English
LAMOTRIGINE [EP]
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
LAMOTRIGINE [USP]
Common Name English
LAMOTRIGINE [WHO-DD]
Common Name English
BW-430C
Code English
LAMOTRIGINE [ORANGE BOOK]
Common Name English
LAMOTRIGINE [USP-RS]
Common Name English
LAMOTRIGINE [USP MONOGRAPH]
Common Name English
LAMOTRIGINE [USAN]
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
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
NDF-RT N0000175751
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
FDA ORPHAN DRUG 91695
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
WHO-ATC N03AX09
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
WHO-VATC QN03AX09
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
NCI_THESAURUS C264
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
NDF-RT N0000008486
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
LIVERTOX 539
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
Code System Code Type Description
PUBCHEM
3878
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
ECHA (EC/EINECS)
281-901-8
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
INN
5638
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
IUPHAR
2622
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
DRUG CENTRAL
1540
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
CAS
84057-84-1
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
RXCUI
28439
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY RxNorm
HSDB
7526
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
NCI_THESAURUS
C38703
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
EPA CompTox
84057-84-1
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
USP_CATALOG
1356756
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY USP-RS
EVMPD
SUB08393MIG
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
LACTMED
Lamotrigine
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
MESH
C047781
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
MERCK INDEX
M6673
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY Merck Index
DRUG BANK
DB00555
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
WIKIPEDIA
LAMOTRIGINE
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
FDA UNII
U3H27498KS
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY
ChEMBL
CHEMBL741
Created by admin on Fri Jun 25 21:01:18 UTC 2021 , Edited by admin on Fri Jun 25 21:01:18 UTC 2021
PRIMARY