Dronedarone (Synonyms:决奈达隆; SR 33589)
目录号 : KM19656 CAS No. : 141626-36-0 纯度 : 98%

Dronedarone (SR 33589) 是胺碘酮 (14187) 的衍生物,是一种用于研究心房颤动 (AF) 的 class III 抗心律失常的试剂 (antiarrhythmic agent)。Dronedarone 是多种离子电流 (ion currents) 的有效阻滞剂,包括钾电流,钠电流,和 L 型钙电流,并通过非竞争性结合到肾上腺素能受体显示出抗肾上腺素能的效果。Dronedarone 是 CYP3A4 的底物和中度抑制剂。

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生物活性

Dronedarone (SR 33589), a derivative of amiodarone (14187), is a class III antiarrhythmic agent for the study of atrial fibrillation (AF) and atrial flutter. Dronedarone is a potent blocker of multiple ion currents, including potassium current, sodium current, and L-type calcium current, and exhibits antiadrenergic effects by noncompetitive binding to β-adrenergic receptors. Dronedarone is a substrate for and a moderate inhibitor of CYP3A4.

体外研究

In patch clamp experiments using human atrial myocytes, Dronedarone produces potent blockade of peak sodium current, resulting in a 97% block at 3 μM.
In guinea pig ventricular myocytes, Dronedarone inhibits the rapidly activating delayed-rectifier potassium current (IC50<3 μM), the slowly activating delayed-rectifier potassium current (IC50=10 μM), the inward rectifier potassium current (IC50>30 μM), and L-type calcium current (IC50=0.18 μM).
Dronedarone exhibits strong inhibitory effects on the acetylcholine-activated potassium current (IK-Ach) in rabbit inoatrial nodal cells (IC50=63 nM) and guinea pig atrial cells (IC50=10 nM). Blockade of IK-Ach by dronedarone is 100 times more potent than that of amiodarone.
Dronedarone exerts its antiadrenergic effects by noncompetitive binding to β-adrenergic receptors (IC50=1.8 μM) and inhibition of agonist-induced increases in adenylate cyclase activity.
Dronedarone (0.01-1 μM) induces a concentration-dependent reduction of coronary perfusion pressure in isolated guinea pig hearts, effects that are independent of the nitric oxide synthase pathway and possibly related to its calcium current blockade.

体内研究

Dronedarone (intraperitoneal injection; 25-100 mg/kg) exhibits anticonvulsant effects in a dose-dependent manner and increases the threshold for electroconvulsions in mice.

Animal Model: Tonic-clonic seizures in male albino Swiss outbred mice
Dosage: 25 mg/kg; 50 mg/kg; 75 mg/kg; 100 mg/kg
Administration: Intraperitoneal injection
Result: Showed significant anticonvulsant effects.
分子式
C31H44N2O5S
分子量
556.76
CAS号
141626-36-0
中文名称
决奈达隆;决奈达龙
运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : ≥ 100 mg/mL (179.61 mM)

* "≥" means soluble, but saturation unknown.

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.7961 mL 8.9805 mL 17.9611 mL
5 mM 0.3592 mL 1.7961 mL 3.5922 mL
10 mM 0.1796 mL 0.8981 mL 1.7961 mL
*

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, 6 months; -20°C, 1 month。-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。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 3 mg/mL (5.39 mM); Clear solution

    此方案可获得 ≥ 3 mg/mL (5.39 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 30.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% corn oil

    Solubility: ≥ 3 mg/mL (5.39 mM); Clear solution

    此方案可获得 ≥ 3 mg/mL (5.39 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 30.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

临床试验
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