Pharmacology Of Lamotrigine

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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.
Pharmacodynamics 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.
Mechanism of action 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 and/or calcium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate). Studies on lamotrigine show binding to sodium channels similar to local anesthetics.
Absorption 98%
Volume of distribution
  • 0.9 to 1.3 L/kg
Protein binding 55%
Metabolism Hepatic
Route of elimination Not Available
Half life 25 +/- 10 hours (healthy individuals); 42.9 hours (chronic renal failure)
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]
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.