N-Desethylamiodarone (hydrochloride)
(Synonyms: 去乙基胺碘酮,N-desethylamiodarone hydrochloride; LB 33020 hydrochloride) 目录号 : GC44346
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N-Desethylamiodarone (hydrochloride)是amiodarone的主要代谢产物，可抑制大鼠中细胞色素P4502D6 (CYP2D6)的活性。
Cas No.:96027-74-6
Sample solution is provided at 25 µL, 10mM.
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N-Desethylamiodarone (hydrochloride) is a major metabolite of amiodarone that inhibits the activity of cytochrome P4502D6 (CYP2D6) in rats [1]. N-Desethylamiodarone inhibits N-methyl-D-aspartic acid (NMDA)-receptor binding in synaptic membranes and enhances intrasynaptosomal free calcium [2]. N-Desethylamiodarone has been widely used to increase the ventricular defibrillation threshold and slow down the conduction speed of Purkinje fibers and ventricular muscle fibers [3].
In vitro, N-Desethylamiodarone treatment for 4 days significantly induced cell death in SGHTL-34 cells, with an EC50 value of 6.8μg/ml [4]. Treatment with 10µM N-Desethylamiodarone for 2 hours significantly enhanced nitric oxide synthase-mediated NO production in human umbilical vein endothelial cells (HUVECs)[5].
In vivo, N-Desethylamiodarone treatment via intravenous injection at a dose of 10mg/kg for 30 minutes, significantly enhanced the ventricular fibrillation threshold in pigs[6]. Intraperitoneal injection of N-Desethylamiodarone at a dose of 25mg/kg every three days for 16 days significantly inhibited melanoma metastasis in mice[7].
References:
[1] Jaruratanasirikul S, Hortiwakul R. The inhibitory effect of amiodarone and desethylamiodarone on dextromethorphan O‐demethylation in human and rat liver microsomes[J]. Journal of pharmacy and pharmacology, 1994, 46(11): 933-935.
[2] Kodavanti P R S, Pentyala S N, Yallapragada P R, et al. Amiodarone and desethylamiodarone increase intrasynaptosomal free calcium through receptor mediated channel[J]. Naunyn-Schmiedeberg's archives of pharmacology, 1992, 345(2): 213-221.
[3] Zhou L, Chen B P, Kluger J, et al. Effects of amiodarone and its active metabolite desethylamiodarone on the ventricular defibrillation threshold[J]. Journal of the American College of Cardiology, 1998, 31(7): 1672-1678.
[4] Beddows S A, Page S R, Taylor A H, et al. Cytotoxic effects of amiodarone and desethylamiodarone on human thyrocytes[J]. Biochemical pharmacology, 1989, 38(24): 4397-4403.
[5] Kishida S, Nakajima T, Ma J, et al. Amiodarone and N-desethylamiodarone enhance endothelial nitric oxide production in human endothelial cells[J]. International Heart Journal, 2006, 47(1): 85-93.
[6] Zhou L, White C M, Chen B P, et al. A comparison of the antifibrillatory effects of desethylamiodarone to amiodarone in a swine model[J]. Journal of cardiovascular pharmacology, 1999, 34(3): 440-445.
[7] Bognar Z, Cseh A M, Fekete K, et al. Amiodarone’s major metabolite, desethylamiodarone inhibits proliferation of B16-F10 melanoma cells and limits lung metastasis formation in an in vivo experimental model[J]. PLoS One, 2020, 15(9): e0239088.
N-Desethylamiodarone (hydrochloride)是amiodarone的主要代谢产物，可抑制大鼠中细胞色素P4502D6 (CYP2D6)的活性[1]。N-Desethylamiodarone可抑制突触膜中N-methyl-D-aspartic acid (NMDA)受体的结合，并提高突触小体内的游离钙含量[2]。N-Desethylamiodarone已被广泛用于提高心室除颤阈值，并减慢浦肯野纤维和心室肌纤维的传导速度[3]。
在体外，N-Desethylamiodarone处理SGHTL-34细胞4天，显著诱导了细胞死亡，EC50值为6.8µg/ml[4]。10µM的N-Desethylamiodarone处理人脐静脉内皮细胞(HUVECs)2小时，显著增强了一氧化氮合酶介导的一氧化氮（NO）产生[5]。
在体内，静脉注射10mg/kg剂量的N-Desethylamiodarone 30分钟，显著提高了猪的心室颤动阈值[6]。每三天腹腔注射25mg/kg剂量的N-Desethylamiodarone，持续16天，显著抑制了小鼠体内黑色素瘤的转移[7]。
| Cell experiment [1]: | |
Cell lines | SGHTL-34 cells |
Preparation Method | SGHTL-34 cells were seeded in 24-well plates at a density of 1×105 cells in Ham’s F12 medium with 5% (v/v) fetal bovine serum (FBS), 16µg/ml gentamicin, 2mM glutamine, 10µg/ml insulin, 10ng/ml somatostatin, 10ng/ml glycine-histidine-lysine acetate, 3.6ng/ml hydrocortisone, 5µg/ml transferrin, and 40µU/ml bovine thyrotrophin at 37°C in 5% CO2/atmosphere. After 4 days of treatment with different concentrations of N-Desethylamiodarone (0, 1, 5, 10, 15, 20, 25, and 30µM), the cell viability was measured. |
Reaction Conditions | 0, 1, 5, 10, 15, 20, 25, and 30µM; 4 days |
Applications | N-Desethylamiodarone treatment significantly inhibited the cell viability of SGHTL-34 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male C57BL/6 mice |
Preparation Method | Male C57BL/6 mice (6 weeks old; 22-25g) were housed singly in a standard environment with food and water ad libitum. B16-F10 cells (5×105/0.1ml) were injected into the lateral tail vein of mice using a 30G 1/2 needle and a 1-ml syringe. Mice were randomly divided into 2 groups of 6 mice each. Each mouse was given a daily intraperitoneal injection of either 100μl 0.9% saline solution containing 10% ethanol as the vehicle control or 25mg/kg N-Desethylamiodarone. Treatment was started one day after cell injection and was given every third day, lasting for consecutive 16 days after injection, when the mice were weighed and sacrificed by cervical dislocation under isoflurane. The lungs were removed for analysis. |
Dosage form | 25mg/kg; every three days for 16 days; i.p. |
Applications | N-Desethylamiodarone treatment significantly reduced lung metastasis formation in mice with B16-F10 xenografts. |
References: | |
| Cas No. | 96027-74-6 | SDF | |
| 别名 | 去乙基胺碘酮,N-desethylamiodarone hydrochloride; LB 33020 hydrochloride | ||
| Canonical SMILES | CCNCCOc1c(I)cc(cc1I)C(=O)c1c(CCCC)oc2ccccc12Cl | ||
| 分子式 | C23H25I2NO3•HCl | 分子量 | 653.7 |
| 溶解度 | DMF: 10 mg/ml,DMSO: 10 mg/ml,Ethanol: 5 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5298 mL | 7.6488 mL | 15.2975 mL |
| 5 mM | 306 μL | 1.5298 mL | 3.0595 mL |
| 10 mM | 153 μL | 764.9 μL | 1.5298 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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- Purity: >98.00% Appearance: A solid
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