2611 Lamotrigine 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. 84057-84-1 3878 C9H7Cl2N5 255.007850 White to pale cream-colored powder. Crystals from isopropanol (T66). 216-218°C (uncorr) 4.88e-01 g/L Inhalation (A308); dermal (A308); ingestion (A308). One proposed mechanism of action of Lamotrigine, the relevance of which remains to be established in humans, involves an effect on sodium channels. <i>in vitro</i> 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. Lamotrigine is metabolized predominantly by glucuronic acid conjugation. The major metabolite is an inactive 2-N-glucuronide conjugate. Exretion occur in the urine and the feces with unchanged lamotrigine (10%), the 2-N-glucuronide (76%), a 5-N-glucuronide (10%), a 2-N-methyl metabolite (0.14%), and other unidentified minor metabolites (4%). (A308) Half Life: 25 +/- 10 hours (healthy individuals); 42.9 hours (chronic renal failure) LD50: 250 (mg/kg) (mice) LD50: 250 (mg/kg) (rat) LD50> 640 (mg/kg) (oral, rat) (Sawyer) LD50> 640 (mg/kg) (oral, mice) (Sawyer) No indication of carcinogenicity to humans (not listed by IARC). 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. Off-label uses include the treatment of peripheral neuropathy, trigeminal neuralgia, cluster headaches, migraines, and reducing neuropathic pain. (A308, L1155) Serious skin rashes, acute multiorgan failure, blood dyscrasias, sudden unexplained death in epilepsy, withdrawal seizures. (A308) May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease. Symptoms of overdose include decreased level of consciousness, coma, delayed heartbeat, increased seizures, lack of coordination, and rolling eyeballs. There are no specific antidotes for lamotrigine. Following a suspected overdose, hospitalization of the patient is advised. General supportive care is indicated, including frequent monitoring of vital signs and close observation of the patient. If indicated, emesis should be induced or gastric lavage should be performed; usual precautions should be taken to protect the airway. (A308) 2009-07-05T03:30:53Z 2014-12-24T20:25:43Z UDP-glucuronosyltransferase 1-4 (UGT1A4) (A308) Lamotrigine 6367 Lamotrigine DB00555 true UDP-glucuronosyltransferase 1-4 (UGT1A4) (A308) NC1=C(N=NC(=N)N1)C1=C(Cl)C(Cl)=CC=C1 C9H7Cl2N5 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) InChIKey=PYZRQGJRPPTADH-UHFFFAOYSA-N 256.091 255.007850663 Exogenous Solid 2.5 HMDB14695 CHEMBL741 3741 <p>Grahame Roy Lee, &#8220;Process for the preparation of lamotrigine.&#8221; U.S. Patent US5925755, issued January, 1981.</p>