| Candidate ID: | R0189 |
| Source ID: | DB00555 |
| Source Type: | approved; investigational |
| Compound Type: |
small molecule
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| Compound Name: |
Lamotrigine
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| Synonyms: |
3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine
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| Molecular Formula: |
C9H7Cl2N5
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| SMILES: |
NC1=NC(N)=C(N=N1)C1=C(Cl)C(Cl)=CC=C1
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| Structure: |
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| DrugBank Description: |
Lamotrigine is an antiepileptic drug belonging in the phenyltriazine class. It is used in the treatment of both epilepsy and as a mood stabilizer in bipolar disorder. Lamotrigine is the first medication since lithium granted Food and Drug Administration (FDA) approval for the maintenance treatment of bipolar type I. It is approved for use in more than 30 countries.
Lamotrigine has relatively few side-effects and does not require laboratory monitoring. While it is indicated for epilepsy and bipolar disorders, there is evidence that lamotrigine could have some clinical efficacy in certain neuropathic pain states.
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| CAS Number: |
84057-84-1
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| Molecular Weight: |
256.091
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| DrugBank Indication: |
Lamotrigine is indicated as adjunctive therapy for the following seizure types in patients ≥2 years of age: partial seizures, primary generalized tonic-clonic seizures, and generalized seizures due to Lennox-Gastaut syndrome.
It is also indicated for the process of conversion to drug monotherapy for those at least 16 years of age or older with partial seizures and currently are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED).
In addition to the above, lamotrigine is also indicated for the maintenance treatment of bipolar I disorder, delaying the time to mood episodes (which may include mania, hypomania, depression, mixed episodes) in adults at least 18 years or older, who have been treated for acute mood symptoms with standard therapy.
Limitations of use
It is important to note that lamotirigine should not be used in the treatment of acute mood episodes, as efficacy has not been established in this context.
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| DrugBank Pharmacology: |
Lamotrigine likely prevents seizures and prevents mood symptoms via stabilizing presynaptic neuronal membranes and preventing the release of excitatory neurotransmitters such as glutamate, which contribute to seizure activity.
A note on cardiovascular effects
The metabolite of lamotrigine, 2-N-methyl metabolite (formed by glucuronidation), is reported to cause dose-dependent prolongations of the PR interval, widening of the QRS complex, and at higher doses, complete AV block. Although this harmful metabolite is only found in trace amounts in humans, plasma concentrations may increase in conditions that cause decreased drug glucuronidation, such as liver disease.
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| DrugBank MoA: |
The exact mechanism of action of lamotrigine is not fully elucidated, as it may exert cellular activities that contribute to its efficacy in a range of conditions. Although chemically unrelated, lamotrigine actions resemble those of phenytoin and carbamazepine, inhibiting voltage-sensitive sodium channels, stabilizing neuronal membranes, thereby modulating the release of presynaptic excitatory neurotransmitters.
Lamotrigine likely acts by inhibiting sodium currents by selective binding to the inactive sodium channel, suppressing the release of the excitatory amino acid, glutamate. The mechanism of action of lamotrigine in reducing anticonvulsant activity is likely the same in managing bipolar disorder. Studies on lamotrigine have identified its binding to sodium channels in a fashion similar to local anesthetics, which could explain the demonstrated clinical benefit of lamotrigine in some neuropathic pain states.
Lamotrigine displays binding properties to several different receptors. In laboratory binding assays, it demonstrates weak inhibitory effect on the serotonin 5-HT3 receptor. Lamotrigine 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. Weak inhibitory effects were observed at sigma opioid receptors. An in vivo study revealed evidence that lamotrigine inhibits Cav2.3 (R-type) calcium currents, which may also contribute to its anticonvulsant effects.
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| Targets: |
Voltage-dependent R-type calcium channel subunit alpha-1E (CACNA1E) inhibitor; Voltage-gated sodium channel alpha subunit inhibitor; Adenosine receptor A1 inhibitor; Adenosine receptor A2a inhibitor; Alpha-1A adrenergic receptor inhibitor; Alpha-2A adrenergic receptor inhibitor; Beta-1 adrenergic receptor inhibitor; D(1) dopamine receptor inhibitor; Dopamine D2 receptor agonist&inhibitor; GABA(A) Receptor antagonist&inducer; GABA(A) Receptor Benzodiazepine Binding Site inhibitor; Histamine H1 receptor antagonist; Kappa-type opioid receptor inhibitor; Acetylcholine receptor subunit alpha inhibitor; 5-hydroxytryptamine receptor 2A inhibitor; 5-hydroxytryptamine receptor 3A inhibitor; Glutamate receptor 1 inhibitor
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| Inclusion Criteria: |
Indication associated
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