HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
Lamotrigine
LAMOTRIGIN · LAMICTAL · 3,5-DIAMINO-6-(2,3-DICHLOROPHENYL)-1,2,4-TRIAZINE · 6-(2,3-DICHLOROPHENYL)-1,2,4-TRIAZINE-3,5-DIAMINE · LTG · TNFSF · BW-430 · PRO726
Identifikatoren & physikalische Daten
| CAS No. | 84057-84-1 |
|---|---|
| Summenformel | C9H7Cl2N5 |
| Durchschnittliche Molmasse | 256,09 g/mol |
| Monoisotopische Masse | 255,00785058 g/mol |
| SMILES | Nc1nnc(-c2cccc(Cl)c2Cl)c(N)n1 |
| InChIKey | PYZRQGJRPPTADH-UHFFFAOYSA-N |
| PubChem CID | 3878 |
| ChEMBL | CHEMBL741 |
| ChEBI | CHEBI:6367 |
| EC No. | 281-901-8 |
| DTXSID | DTXSID2023195 |
Chemische & physikalische Eigenschaften
| XLogP | 1,4 |
|---|---|
| Polarare Oberfläche (TPSA) | 90,7 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 5 |
| Frei drehbare Bindungen | 1 |
| Schwere Atome | 16 |
| Formalladung | 0 |
| Komplexität | 242 |
| Arzneimittel | PharmaceuticalsPharmaceuticals -> AntiepilepticPharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Used in Switzerland |
| LogP (Verteilungskoeffizient) | log Kow = 2.571.6 |
| Color/Form | White to pale cream-colored powder. Crystals from isopropanol |
| Löslichkeit | In water, 170 mg/L at 25 °CSolubility in 0.1M hydrochloric acid: 4.1 mg/mL at 25 °C4.88e-01 g/LDMSO: 20 mg/mL at 60 °C, soluble |
| Human Drugs | Breast FeedingLactationMilk, HumanAnticonvulsantsAntimanic AgentsAntidepressive AgentsFDA approved drugs -> Active ingredientPharmaceuticalsAntiseizure medicines |
| Siedepunkt | 503.1±60.0503.1±60.0 °C(Predicted) |
| Schmelzpunkt | 177-181216-218 °C (uncorr)216 - 218 °C (uncorr.)177-181°C |
| Physical Description | Solid |
| Dissociation Constants | 5.7pKa = 5.7 |
| Collision Cross Section | 150.6 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]149.56 Ų [M+H]+ [CCS Type: TW151.2 Ų [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)] |
| Dichte | 1.572±0.06 g/cm3(Predicted) |
| Flammpunkt | 9℃ |
| Lagerbedingungen | 2-8°C |
| pKa (Säurekonstante) | 5.7(at 25℃) |
| Aggregatzustand | powder |
| Farbe | white |
| Merck | 14,5353 |
| BCS Class | 2 |
| InChI | 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 |
| SMILES | N1C(C2=CC=CC(Cl)=C2Cl)=C(N)N=C(N)N=1 |
| CAS Datenbank | 84057-84-1(CAS DataBase Reference) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]P264, P270, P273, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 68 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation] |
|---|---|
| Regulatorische Informationen | Lamotrigine: Does not have an individual approval but may be used under an appropriate group standard |
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including lamotrigine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Toxic Combustion Products | Special hazards arising from the substance or mixture: Carbon oxides, nitrogen oxides (NOx), Hydrogen chloride gas |
| Hazard Classes and Categories | Acute Tox. 3 (100%) |
| Brandbekämpfungsverfahren | Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. |
| Lagerbedingungen | Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: 2 - 8 degC Keep in a dry place. |
| Reinigungsverfahren | ACCIDENTAL RELEASE MEASURES. Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.Methods and materials for containment and cleaning up Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. |
| Entsorgungsverfahren | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator. |
| Preventive Measures | Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. |
| Personal Protective Equipment (PPE) | Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).Body Protection: Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.Skin protection: Handle with gloves.Eye/face protection: Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). |
| Treatment | 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 performedusual precautions should be taken to protect the airway. (A308) |
| Wechselwirkungen | Rash, including serious and potentially life-threatening rash, appears to be more likely to occur in patients receiving concomitant valproic acid. Valproic acid can decrease clearance and increase plasma concentrations of lamotrigine more than twofoldexceeding the recommended reduced initial dosage of lamotrigine or the subsequent recommended schedule for escalation of lamotrigine dosage, particularly in patients receiving valproic acid, may increase the incidence of rash, including serious rash, in lamotrigine-treated patients. In clinical trials, 1% of adults and 1.2% of children receiving a drug regimen including immediate-release lamotrigine concomitantly with valproic acid experienced a rash requiring hospitalization, while 0.16% of adults and 0.6% of children receiving a drug regimen of lamotrigine without valproic acid were hospitalized because of rash.The concomitant use of valproic acid and/or hepatic enzyme-inducing anticonvulsant drugs (e.g., phenobarbital, primidone, carbamazepine, phenytoin) can increase or decrease the metabolism and elimination of lamotrigine, requiring dosage adjustments to maintain efficacy and/or avoid toxicity. Addition of valproic acid to lamotrigine therapy reduces lamotrigine clearance and increases steady-state plasma lamotrigine concentrations by slightly more than 50% whether or not hepatic enzyme-inducing anticonvulsant drugs are given concomitantly. Conversely, steady-state plasma concentrations of lamotrigine are decreased by about 40% when phenobarbital, primidone, or carbamazepine is added to lamotrigine therapy and by about 45-54% when phenytoin is added to lamotrigine therapythe magnitude of the effect with phenytoin is dependent on the total daily dosage of phenytoin (from 100-400 mg daily). Discontinuance of an enzyme-inducing anticonvulsant drug can be expected to increase, and discontinuance of valproic acid can be expected to decrease, the elimination half-life and plasma concentrations of lamotrigine. Although the manufacturers state that a therapeutic plasma concentration range has not been established for lamotrigine and that dosage should be based on therapeutic response, the change in plasma lamotrigine concentrations resulting from addition or discontinuance of enzyme-inducing anticonvulsant drugs or valproic acid should be considered when these drugs are added to or withdrawn from an existing anticonvulsant drug regimen that includes lamotrigine.Addition of lamotrigine to existing therapy with phenytoin or carbamazepine generally does not appreciably alter the steady-state plasma concentrations of these concomitantly administered drugs. Addition of lamotrigine to carbamazepine therapy reportedly has resulted in increased plasma concentrations of a pharmacologically active metabolite of carbamazepine (carbamazepine-10,11-epoxide) and an increased incidence of some adverse effects (e.g., dizziness, headache, diplopia, blurred vision, ataxia, nausea, nystagmus). However, elevations in carbamazepine-10,11-epoxide plasma concentrations and/or increased toxicity have not been consistently observed with concomitant administration of lamotrigine and carbamazepine, and the mechanism of the interaction between these drugs remains unclear.Addition of lamotrigine to valproic acid therapy in healthy individuals resulted in a 25% reduction in trough steady-state plasma concentrations of valproic acid over a 3-week period, followed by stabilization of these concentrations.For more Interactions (Complete) data for LAMOTRIGINE (11 total), please visit the HSDB record page. |
| Gesundheitliche Auswirkungen | 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. |
| Hepatotoxicity | Prospective studies suggest that less than 1% of subjects develop elevations in serum aminotransferase levels during long term lamotrigine therapy. However, clinically apparent hepatotoxicity from lamotrigine is well known and is estimated to occur in one in 2,000 to 10,000 treated patients. The liver injury is usually part of a systemic immuno-allergic reaction (anticonvulsant hypersensitivity syndrome [AHS] or drug rash with eosinophilia and systemic symptoms [DRESS] syndrome). The latency is typically short, ranging from one to several weeks. Presenting symptoms are a diffuse maculopapular rash, followed in a few days by high fever, nausea and vomiting. The rash can develop into a systemic hypersensitivity reaction and multiorgan failure or be associated with jaundice and hepatitis. Eosinophilia is common, and facial edema, lymphadenopathy and atypical lymphocytosis can occur. The pattern of liver enzyme elevations is usually hepatocellular and severity ranges from mild-to-moderate ALT elevations accompanying the generalized hypersensitivity reaction, to an icteric hepatitis, to a severe hepatitis and acute liver failure. Liver biopsy shows portal inflammation, hepatocellular necrosis and bile duct proliferation. In some instances of severe hypersensitivity syndrome with acute multiorgan failure, the hepatic involvement may represent ischemic injury. |
| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1900(SRC), determined from a structure estimation method(2), indicates that lamotrigine is expected to have low mobility in soil(SRC). The pKa1 and pKa2 of lamotrigine are 8.53 and 9.21(3), respectively, indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of lamotrigine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.2X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Lamotrigine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.4X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2015).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1900(SRC), determined from a structure estimation method(2), indicates that lamotrigine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.2X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 23(SRC), from its log Kow of 2.57(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2015).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), lamotrigine, which has an estimated vapor pressure of 9.4X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase lamotrigine may be removed from the air by wet and dry deposition(SRC). Lamotrigine does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC). |
| Unerwünschte Wirkungen | United States Boxed Warning: Lamotrigine can cause serious rashes requiring hospitalization and discontinuation of this medication. Rash severity varies but includes a risk for Stevens-Johnson syndrome. The incidence of Stevens-Johnson syndrome in the pediatric population is 0.3%-0.8%, and 0.03%-0.08% in adults. The number of cases associated with toxic epidermal necrolysis is too low to report an estimated incidence. Nearly all cases of a rash occur 2 to 8 weeks after the initiation of lamotrigine. It should also be noted that discontinuing lamotrigine may not prevent a rash from becoming life-threatening. Patient education should include continuous monitoring of the rash for improvement after discontinuing the medication. |
| Expositionspfade | Inhalation (A308)dermal (A308)ingestion (A308). |
| Milk Concentrations | Lamotrigine is distributed into breast milk. |
| Toxizitätsübersicht | IDENTIFICATION AND USE: Lamotrigine is a white to pale cream-colored powder. Lamotrigine is an anticonvulsant medication that also has utility in the treatment of bipolar disorder. HUMAN EXPOSURE AND TOXICITY: Lamotrigine has been associated with many side effects, including rashes that can progress to Stevens-Johnson syndrome or toxic epidermal necrolysis. It has also been associated with the development of motor tics, most commonly in the head, neck, and shoulders. Cases of life-threatening rashes associated with lamotrigine almost always have occurred within 2-8 weeks of treatment initiationhowever, severe rashes rarely have presented following prolonged treatment (e.g., 6 months). Lamotrigine-associated rashes do not appear to have distinguishing features. Because it is not possible to distinguish benign rashes from those that may become severe and/or life-threatening, lamotrigine generally should be discontinued at the first sign of rash (unless the rash is known not to be drug related). However, a rash may become life-threatening or permanently disabling or disfiguring despite discontinuance of the drug. Discontinuance of lamotrigine because of rash was required in 3% of adults receiving the drug as adjunctive therapy and 4.5% of adults receiving the drug as monotherapy in controlled clinical trials4.4% of pediatric patients receiving lamotrigine in controlled clinical trials discontinued the drug because of the development of rash. Multiorgan failure and various degrees of hepatic failure, in some cases fatal, have been reported rarely with lamotrigine as adjunctive therapy. The possibility of such potentially fatal adverse effects should be considered in patients who exhibit signs and symptoms associated with multiorgan and/or hepatic impairment following initiation of lamotrigine as adjunctive therapy. During the premarketing development of lamotrigine, 20 sudden and unexplained deaths were reported among a cohort of 4700 patients with epilepsy receiving adjunctive therapy with the drug (5747 patient-years of exposure). Although the rate of these deaths exceeds that expected to occur in a healthy (nonepileptic) population matched for age and gender, this rate was similar to that occurring in a similar population of epileptic patients receiving a chemically unrelated anticonvulsant agent. Among 414 first-trimester exposures to lamotrigine monotherapy, 12 outcomes with major birth defects were reported. Among the 88 first-trimester exposures to lamotrigine polytherapy including valproate, 11 outcomes with major birth defects were reported. Among 182 first-trimester exposures to lamotrigine polytherapy excluding valproate, 5 outcomes with major birth defects were reported. No distinctive pattern of major birth defects was apparent among the offspring exposed to lamotrigine monotherapy or polytherapy. The risk of all major birth defects after first-trimester exposure to lamotrigine monotherapy (2.9%) was similar to that in the general population and in other registries enrolling women exposed to antiepileptic monotherapy (3.3% to 4.5%). Lamotrigine also did not increase the incidence of structural or numerical chromosomal abnormalities in the in vitro human lymphocyte assay. ANIMAL STUDIES: In animal studies, no evidence of carcinogenicity was seen following oral administration of lamotrigine for up to 2 years at maximum tolerated doses (30 mg/kg of body weight per day in mice and 10 to 15 mg/kg per day in rats). Lamotrigine administered i.p. at high doses can induce intrauterine growth retardation and at low multiple doses causes a dose-dependent increase in embryonic resorption, craniofacial and caudal malformations as well as maternal toxicity in the mouse. A study of the teratogenic activity of lamotrigine was carried out in the brain of fetuses of rats who had received the drug. Results showed that fetuses of the experimental group had reduced body weight at birth, increased volume and diameter of the cerebral structure, increased density of the subcortical layer, and ventricle dilatation. A behavioral teratology study was conducted in rats dosed during the period of organogenesis. At day 21 postpartum, offspring of dams receiving 5 mg/kg per day or higher displayed a significantly longer latent period for open field exploration and a lower frequency of rearing. In a swimming maze test performed on days 39 to 44 postpartum, time to completion was increased in offspring of dams receiving 25 mg/kg per day. No evidence of mutagenicity was demonstrated by lamotrigine in vitro in the Ames Salmonella microbial mutagen test or the mammalian mouse lymphoma assay. Lamotrigine also did not increase the incidence of structural or numerical chromosomal abnormalities in the in vivo rat bone marrow assay.With excessive lamotrigine overdoses, some reportedly as high as 16 g, fatalities have occurred following complications, including seizures, coma, and conduction abnormalities. Immediate-release lamotrigine is rapidly absorbed, and inducing emesis may not be the appropriate intervention in this instance. However, hospitalization and supportive care are indicated, along with the usual airway-protective precautions. As of this writing, there is no known specific antidote for lamotrigine toxicity.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. |
| Signs and Symptoms | Symptoms of overdose include decreased level of consciousness, coma, delayed heartbeat, increased seizures, lack of coordination, and rolling eyeballs. |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of lamotrigine can be estimated to be 1900(SRC). According to a classification scheme(2), this estimated Koc value suggests that lamotrigine is expected to have low mobility in soil. The pKa1 and pKa2 of lamotrigine are 8.53 and 9.21(3), respectively, indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). |
| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ Cases of life-threatening rashes associated with lamotrigine almost always have occurred within 2-8 weeks of treatment initiationhowever, severe rashes rarely have presented following prolonged treatment (e.g., 6 months). Lamotrigine-associated rashes do not appear to have distinguishing features. Because it is not possible to distinguish benign rashes from those that may become severe and/or life-threatening, lamotrigine generally should be discontinued at the first sign of rash (unless the rash is known not to be drug related). However, a rash may become life-threatening or permanently disabling or disfiguring despite discontinuance of the drug. Discontinuance of lamotrigine because of rash was required in 3% of adults receiving the drug as adjunctive therapy and 4.5% of adults receiving the drug as monotherapy in controlled clinical trials4.4% of pediatric patients receiving lamotrigine in controlled clinical trials discontinued the drug because of the development of rash. The potential for development of a rash at the beginning of lamotrigine therapy may be decreased by employing low initial dosages and by gradual escalation of dosage to avoid initially high plasma concentrations of the drug./SIGNS AND SYMPTOMS/ Rashes severe enough to cause hospitalization, including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, angioedema, and a hypersensitivity syndrome (usually consisting of fever, rash, facial swelling, and hematologic, hepatic, and/or lymphatic involvement), occurred in 0.3% of adults receiving lamotrigine in premarketing controlled and uncontrolled clinical trials and in about 0.8% of pediatric patients receiving the drug in clinical trialsdeath associated with rash has been reported rarely in postmarketing use of lamotrigine. Erythema multiforme has been reported in patients receiving lamotrigine in premarketing controlled and uncontrolled clinical trials in the US, while lupus-like syndrome and vasculitis have been reported during postmarketing experience with the drug and/or in worldwide uncontrolled clinical trials./CASE REPORTS/ ... The finding of Stevens-Johnson syndrome in two cases out of three treated with lamotrigine plus aripiprazole, however, has a much higher index of suspicion and it is correct to warn of its possible raised risk. .../CASE REPORTS/ A young woman receiving concomitant valproic acid and carbamazepine developed a possible hypersensitivity syndrome consisting of headache, fever, and a maculopapular rash 3 weeks following addition of lamotrigine to therapyfulminant hepatic failure and hepatic coma developed within 3 days, and despite subsequent clinical improvement, the patient died of a massive pulmonary embolus 2 months later.For more Human Toxicity Excerpts (Complete) data for LAMOTRIGINE (48 total), please visit the HSDB record page. |
| Wassergefährdungsklasse (WGK) | 3 |
| UN-Transportnummer | UN 2811 6.1/PG 3 |
| Zollcode | 29336990 |
| RTECS-Nr. | XY5850700 |
| R-Sätze (R) | 25-36/37/38-39/23/24/25-23/24/25-11 |
| Toxizität | LD50 in mice, rats (mg/kg): 250, >640 orally (Sawyer) |
| Gefahrensymbole | T,Xi,F |
| Sicherheitshinweise (S) | 45-36-26-36/37-16 |
| Gefahrenklasse | 6.1(b)Acute Tox. 3 Oral |
| Verpackungsgruppe | III |
| Lagerklasse | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| Gefahrstoffdaten | 84057-84-1(Hazardous Substances Data) |
Anwendungen & Verwendung
Beschreibung
Lamotrigine, also known by the brand name Lamictal®, is a second-generation antiepileptic drug (AED) manufactured by GlaxoSmithKline in the UK and USA. Lamotrigine is a new mazine, glutamate inhibitor anticonvulsant that significantly reduces the incidence of refractory partial seizures. The drug is reported to produce fewer CNS side effects than diazepam or sodium phenytoin. It is also indicated as add-on therapy for the treatment of generalized seizures not satisfactorily controlled by other anti-epileptics.
History
The development of lamotrigine began in the early 1980s, accidentally discovered by a group of chemists at the Wellcome Research Laboratory while searching for novel antifolate compounds. Initially synthesized as an antifolate analog, subsequent animal model screening revealed its significant anticonvulsant activity, demonstrating its potential as an antiepileptic drug. In 1980, the Wellcome Foundation filed the first synthetic method and related patent applications for lamotrigine (e.g., European Patent EP 0021121), mentioning researchers such as M. G. Baxter. During clinical development, the efficacy of lamotrigine (trade name: lamotrigine tablets) was confirmed, and it was first launched in Ireland in 1991. Subsequently, it was approved by the U.S. Food and Drug Administration (FDA) for the treatment of epilepsy in 1994. In subsequent studies, the clinical applications of lamotrigine have continued to expand, particularly its efficacy as a mood stabilizer. Researchers such as Richard H. Weissler have advanced the application of lamotrigine in the treatment of bipolar disorder, especially in the maintenance treatment of bipolar depression, through clinical observation and research.
Verwenden
Lamotrigine is an anticonvulsant that works by Inhibits glutamate release, possibly through inhibition of Sodium, Potassium, and Calcium currents. Used in the treatment of bipolar depression, partial seizures in epilepsy, and generalized seizures of Lennox-Gastaut syndrome. Additionally, it is used for the maintenance treatment of bipolar I disorder and depression.
Herstellung & Synthese
synthetische
The preparation method of Lamotrigine involves several steps. 2,3-dichlorobenzoic acid is chlorinated to 2,3-dichlorobenzoyl chloride, then reacted with cuprous cyanide, condensed with aminoguanidine, and finally cyclized under the action of potassium hydroxide Lamotrigine.Two key methods for the synthesis of lamotrigine have been reported.https://www.sciencedirect.com/topics/chemistry/lamotrigine A novel process for the synthesis of lamotrigine and its intermediatehttps://patents.google.com/patent/WO2007069265A1/en