化合物信息

Drug Groups

approved; investigational

Description

Lamotrigine is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. For epilepsy it is used to treat partial seizures, primary and secondary tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome. Lamotrigine also acts as a mood stabilizer. It is the first medication since lithium granted Food and Drug Administration (FDA) approval for the maintenance treatment of bipolar type I. Chemically unrelated to other anticonvulsants, lamotrigine has relatively few side-effects and does not require blood monitoring. The exact way lamotrigine works is unknown. [Wikipedia]

Indication

For the adjunctive treatment of partial seizures in epilepsy and generalized seizures of Lennox-Gastaut syndrome. Also for the maintenance treatment of bipolar I disorder and depression.

Pharmacology

Lamotrigine, an antiepileptic drug (AED) of the phenyltriazine class, is chemically unrelated to existing antiepileptic drugs. Lamotrigine is also used in the treatment of depression and bipolar disorder. 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.

Toxicity

LD₅₀=250 (mg/kg) (in rat, mice); LD₅₀>640 orally (mg/kg) (in rat, mice) (Sawyer). Symptoms of overdose include decreased level of consciousness, coma, delayed heartbeat, increased seizures, lack of coordination, and rolling eyeballs.

Affected Organisms

Biotransformation

Hepatic

Absorption

98%

Half Life

25 +/- 10 hours (healthy individuals); 42.9 hours (chronic renal failure)

Protein Binding

55%

Distribution

* 0.9 to 1.3 L/kg

Clearance

* Apparent plasma cl=0.44 mL/min/kg [healthy volunteers taking single-dose LAMICTAL]
* Apparent plasma cl=0.58 mL/min/kg [healthy volunteers taking multiple-dose LAMICTAL]
* Apparent plasma cl=0.30 mL/min/kg [healthy volunteers taking valproate and single-dose LAMICTAL]
* Apparent plasma cl=0.18 mL/min/kg [healthy volunteers taking valproate and multiple-dose LAMICTAL]
* Apparent plasma cl=1.1 mL/min/kg [Patients with epilepsy taking carbamazepine, phenytoin, phenobarbital, or primidone plus valproate and single-dose LAMICTAL]
* Apparent plasma cl=1.12 mL/min/kg [Patients with epilepsy taking carbamazepine, phenytoin, phenobarbital, or primidone plus valproate and multiple-dose LAMICTAL]

References

External Links