General
Preferred name
LAMOTRIGINE
Synonyms
BW430C ()
LTG ()
Lamotrigine isethionate ()
Lamictal ()
BW-430C,LTG ()
NSC-759171 ()
Lamictal Cd ()
BW 430C ()
Lamictal Odt ()
BW-430C ()
Lamictal Xr ()
Lamotrigine-d3 ()
P&D ID
PD000352
CAS
113170-86-8
84057-84-1
1132746-94-1
Tags
natural product
drug
available
Approved by
FDA
First approval
1994
Drug Status
investigational
approved
Drug indication
Anticonvulsant
Epilepsy
Bipolar disorder
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
MOA Although chemically unrelated, lamotrigine resembles the actions of phenytoin and carbamazepine in inhibiting voltage-sensitive sodium channes thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids such as glutamate and aspartate [FDA Label]. Studies on lamotrigine show binding to sodium channels similar to local anesthetics, which could explain potential clinical benefit of lamotrigine in some neuropathic pain states [T28]. ; ; Lamotrigine displays binding properties to several different receptors. It mediates a weak inhibitory effect on serotonin 5-HT3 receptor with IC50 of 18 µM [FDA Label]. It also weakly binds to Adenosine A1/A2 receptors, α1/α2/β adrenergic receptors, dopamine D1/D2 receptors, GABA A/B receptors, histamine H1 receptors, κ-opioid receptor (KOR), mACh receptors and serotonin 5-HT2 receptors with an IC50>100 µM [FDA Label]. Lamotrigine had weak effects at sigma opioid receptors (IC50 = 145 µM) [FDA Label]. A study demonstrated an evidence _in vivo_ that lamotrigine inhibits Cav2.3 (R-type) calcium currents that could also contribute to its anticonvulsant activity [A31737]. This inhibition of calcium currents is also observed in topiramate.
INDICATION Indicated as adjunctive therapy for the following seizure types in patients ≥2 years of age: partial seizures/primary generalized tonic-clonic seizures/generalized seizures of Lennox-Gastaut syndrome [FDA Label].; ; Indicated for conversion to monotherapy in adults (≥16 years of age) with partial seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED)[FDA Label]. ; ; 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 (≥18 years of age) treated for acute mood episodes with standard therapy [FDA Label].
DESCRIPTION Lamotrigine is an anticonvulsant drug. (GtoPdb)
PHARMACODYNAMICS Lamotrigine, an antiepileptic drug (AED) of the phenyltriazine class, is chemically unrelated to existing antiepileptic drugs. Lamotrigine displays a broader therapeutic profile than earilier antiepileptic drugs with significant efficacy against absence seizures [T28]. Lamotrigine is thought to exert its anticonvulsant effect by stabilizing presynaptic neuronal membranes. Lamotrigine inhibits sodium currents by selectively binding to the inactivated state of the sodium channel and subsequently suppresses the release of the excilatory amino acid, glutamate. The mechanism of action of lamotrigine in reducing anticonvulsant activity is assumed to be the same for reducing biopolar depression. Lamotrigine demonstrates effectiveness in preventing the recurrence of mania and depression [T28].; ; Lamotrigine binds to melanin-containing tissues such as eyes and pigmented skin [FDA Label]. The metabolite of lamotrigine formed by glucuronidation, 2-N-methyl metabolite, is reported to cause dose-dependent prolongations of the PR interval, widening of the QRS complex, and, at higher doses, complete AV conduction block. Although the metabolite is only found in trace amounts in humans, the plasma concentrations of this metabolite may be increased in conditions where the extent of glucuronidation is reduced, such as liver disease [FDA Label].
TOXICITY Some fatal cases of overdose involving quantities up to 15 g have been reported. Overdose has resulted in ataxia, nystagmus, increased seizures, decreased level of consciousness, coma, and intraventricular conduction delay. While there is no known antidote for lamotrigine, hospitalization and general supportive care is recommended in case of suspected overdose. If indicated, gastric lavage and emesis may be required with appropriate precautions made to protect the airway. It is uncertain whether hemodialysis is an effective means of removing lamotrigine from the blood [FDA Label].; ; Oral TDLO in man is 19 mg/kg and oral TDLO (intermittent) in woman is 2 mg/kg/30H [MSDS]. Oral LD50 in mouse and rat is 205 mg/kg and 245 mg/kg, respectively [MSDS]. In animal studies, lamotrigine was not found to be teratogenic. However it decreased fetal folate concentrations in rats, an effect known to be associated with teratogenesis in animals and humans [FDA Label]. There is no evidence of carcinogenic or mutagenic potential for lamotrigine and effect of lamotrigine on human fertility is unknown [FDA Label].
DESCRIPTION Potent and selective 5-HT7 antagonist; brain penetrant (Tocris Bioactive Compound Library)
DESCRIPTION Anticonvulsant (LOPAC library)
DESCRIPTION High affinity and selective M2 antagonist (Tocris Bioactive Compound Library)
DESCRIPTION Lamotrigine isethionate can inhibit glutamate release. It also shows anticonvulsant effects. It is an antiepileptic. (BOC Sciences Bioactive Compounds)
Cell lines
0
Organisms
1
Compound Sets
30
AdooQ Bioactive Compound Library
A11873
Axon Medchem Screening Library
1353
BOC Sciences Bioactive Compounds
lamotrigine-isethionate-cas-113170-86-8-item-83753
Cayman Chemical Bioactives
15428
37196
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
CHEMBL741
ChEMBL Drugs
CHEMBL741
Drug Repurposing Hub
DrugBank
DB00555
DrugBank Approved Drugs
DB00555
DrugCentral
1540
DrugCentral Approved Drugs
1540
DrugMAP
DM8SXYG
DrugMAP Approved Drugs
DM8SXYG
DrugMatrix
Enamine BioReference Compounds
Guide to Pharmacology
2622
LOPAC library
MedChem Express Bioactive Compound Library
HY-B0495
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
U3H27498KS
NIH Clinical Collections (NCC)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
lamotrigine
TargetMol Bioactive Compound Library
T0680
The Spectrum Collection
Tocris Bioactive Compound Library
1611
2289
VGSC-DB
NA0026
NA0027
NA0028
NA0029
NA0030
NA0031
NA0032
NA0033
NA0034
NA0035
NA0036
NA0037
NA5924
External IDs
49
Properties
(calculated by RDKit )
Molecular Weight
255.01
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
2
Rotatable Bonds
1
Ring Count
2
Aromatic Ring Count
2
cLogP
2.01
TPSA
90.71
Fraction CSP3
0.0
Chiral centers
0.0
Largest ring
6.0
QED
0.81
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
MOA
voltage-gated sodium channel blocker
serotonin receptor antagonist, sodium channel blocker
Target
Sodium channel alpha subunit
5-HT (human platelets)
5-HT (rat brain synaptosomes)
SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN7A, SCN8A, SCN9A
Glutamate antagonist
Sodium Channel
5-HT Receptor,Sodium Channel
Pathway
GPCR/G protein
Neuroscience
Autophagy
Membrane Transporter/Ion Channel
Primary Target
Miscellaneous Glutamate
Indication
epilepsy, bipolar disorder
Therapeutic Indication
Anticonvulsant
Therapeutic Class
CNS & PNS
Anticonvulsants
VGSC Target
Nav1.2
Nav1.3
Nav1.5
Nav1.7
Nav1.8
Nav1.9
Source data