Retigabine Dihydrochloride
Retigabine Dihydrochloride
CAS: 150812-13-8
Molecular Formula: C16H19ClFN3O2
Retigabine Dihydrochloride - Names and Identifiers
| Name | Retigabine Dihydrochloride |
| Synonyms | D 20443 Retigabine HCl Retigabine 2HCL D20443 dihydrochloride D 20443 dihydrochloride Retigabine Dihydrochloride ethyl {2-amino-4-[(4-fluorobenzyl)amino]phenyl}carbamate hydrochloride ethyl {2-amino-4-[(4-fluorobenzyl)amino]phenyl}carbamate dihydrochloride Ethyl [2-amino-4-[[(4-fluorophenyl)methyl]amino]phenyl]carbamate Dihydrochloride N-(2-Amino-4-(4-fluorobenzylamino)phenyl)carbamic Acid Ethyl Ester Dihydrochloride |
| CAS | 150812-13-8 |
| EINECS | 2017-001-1 |
| InChI | InChI=1/C16H18FN3O2.ClH/c1-2-22-16(21)20-15-8-7-13(9-14(15)18)19-10-11-3-5-12(17)6-4-11;/h3-9,19H,2,10,18H2,1H3,(H,20,21);1H |
Retigabine Dihydrochloride - Physico-chemical Properties
| Molecular Formula | C16H19ClFN3O2 |
| Molar Mass | 339.8 |
| Melting Point | 168-170°C |
| Boling Point | 430°C at 760 mmHg |
| Flash Point | 213.9°C |
| Vapor Presure | 1.34E-07mmHg at 25°C |
| Storage Condition | Hygroscopic, -20°C Freezer, Under Inert Atmosphere |
| In vitro study | Retigabine is a new antiepileptic drug whose mechanism is mainly the activity of opening potassium channels in neuronal cells. Retigabine can significantly enhance the current of KCNQ2/Q3. In addition, retigabine can also enhance slow channel inactivation. In rat hippocampal slices, Retigabine increased GABA synthesis; In cultured rat cortical neurons, enhanced GABA-induced chloride currents. In rat hippocampal Entorhinal Cortex Slices, Retigabine induces neuronal membrane hyperpolarization and opens potassium channels in neuronal cells. In differentiated PC12 cells, Retigabine enhances linopirdine-sensitive currents. To significantly improve the response of GABAA receptor, the concentration of RTG/EZG should be greater than 10 μm. Different GABAA receptor and different combinations of subunits have different effects on RTG/EZG, according to the strong to weak order of its effectiveness: Alpha 1 beta 3 Gamma 2 = alpha 1 beta 2 Gamma 2> Alpha 3 beta 2 Gamma 2 = alpha 2 Beta 2 Gamma 2> Alpha 5 Beta 2 Gamma 2 = alpha 1 beta 2(N265S) Gamma 2 = alpha 1 beta 1 Gamma 2. RTG/EZG at higher than therapeutic concentrations had only a weak inhibitory effect on voltage-gated Nav and Cav channel currents, and RTG/EZG had no significant interaction with glutamate receptors. |
| In vivo study | Retigabine enhances GABA energy transmission in the central nervous system. Retigabine is rapidly dispersed and absorbed in the body with an oral bioavailability of 60% and a volume of distribution of about 6.2 L/kg. It is well tolerated in humans at titrant doses up to 600-1200 mg/kg. The plasma protein binding rate of the drug is about 80%. The oral route of administration has a high systemic bioavailability, indicating that Retigabine is resistant to first-pass metabolism. Retigabine is metabolized by stage Ⅱ hepatic glucosidation and acetylation. The effect of Retigabine is sex-specific, with females having higher plasma concentrations of the drug after oral administration of Retigabine compared to males. The excretion of Retigabine is mainly through the kidneys. Through the analysis of the behavior node found that in mice and rats, intraperitoneal injection of Retigabine administration, retigabine has a poor therapeutic index (therapeutic index = TD50 obtained in the rotation experiment/ED50 obtained in the maximum electric shock experiment, and the maximum tonic extension of the lower limb is selected as the node). However, the therapeutic index was 28.8 after oral administration in rats, which compares favorably with other antiepileptic drugs such as carbamazepine. |
