Hydroquinidine   中文名称: 二氢奎尼丁

Hydroquinidine is a class Ia antiarrhythmic drug. The study mentions it inhibits the transient outward potassium current (I_to) of the cardiac action potential, which is implicated in Brugada syndrome. [2]

这项临床研究证明了长期氢奎尼丁治疗对短QT综合征（SQTS）患者的体内（人体）疗效。在17名接受治疗的患者中，氢奎尼丁（平均剂量584 ± 53 毫克/天）显著延长了QTc间期，从基线331 ± 3毫秒延长至391 ± 5毫秒（平均延长60 ± 6毫秒；p < 0.001）。
在对15名长期治疗患者（平均6 ± 1年）的匹配周期分析中，发生危及生命的心律失常事件（LAE：心脏骤停或心源性猝死）的患者比例从治疗前相等时期的40%降至治疗期间的0%（p = 0.03）。每名患者的LAE数量从0.73 ± 0.30次降至0次（p = 0.026）。
在另一项针对16名既往心脏骤停存活的SQTS患者的分析中，LAE的年发生率从未治疗时的12%（82人年发生10次事件）降至接受氢奎尼丁治疗期间的0%（44人年发生0次事件）（p = 0.028）。[1]
这项临床研究（人体）评估了氢奎尼丁在Brugada综合征（BrS）患者中的疗效。
在接受电生理（EP）指导治疗的无症状且可诱发室性心动过速/心室颤动（VT/VF）的BrS患者（n=29）中，氢奎尼丁（平均剂量 609 ± 89 毫克/天）在22名患者（76%）中预防了VT/VF的诱发。[2]
在接受长期氢奎尼丁治疗（平均随访 17 ± 13 个月）的21名无症状、可诱发患者中，17名（81%）保持无症状。两名患者在随访期间出现晕厥；一例与QTc间期显著延长（530 ms）和记录到的非持续性VT发作有关，另一例原因不明但可能与不依从用药有关。另外两名患者因晚期胃肠道不耐受而停用氢奎尼丁。[2]
在另一组10名无症状、可诱发、因持续可诱发或早期不耐受而接受植入式心律转复除颤器（ICD）治疗（而非长期氢奎尼丁）的患者中，平均随访13 ± 8个月期间发生了一次适当的ICD电击。[2]
在四名有多次适当ICD电击史的症状性BrS患者中，长期氢奎尼丁治疗在平均14 ± 8个月的随访期内，所有病例均预防了电击复发和VT/VF发作。其中一名患者记录到室性心律失常连发显著减少。[2]

The study monitored plasma levels of Hydroquinidine. The mean plasma level in treated patients was 2.7 ± 3.3 µmol/L. The stated usual therapeutic concentration range (by fluorimetry) is 3 to 6 µmol/L.
Dose adjustments were made based on plasma levels and electrophysiologic study results. The standard dose was a "slow-release" preparation of 300 mg twice daily (600 mg/day). The dose was increased to 900 mg/day if VT/VF remained inducible and the plasma level was below 3 µmol/L. [2]

In this study, Hydroquinidine therapy was generally well-tolerated. Two out of 17 patients (12%) discontinued treatment within one week due to gastrointestinal intolerance (diarrhea). No pro-arrhythmic events were observed during the treatment period. The study mentions that the tolerability profile was better than in a previous study on Brugada syndrome, possibly due to the lower mean daily dose used (584 ± 53 mg/day vs. 738 ± 25 mg/day). [1]
During the trial period, drug intolerance occurred in 7 of 35 patients (20%), primarily diarrhea, leading to Hydroquinidine withdrawal in 2 patients.
One patient experienced a reversible Hydroquinidine-induced hepatitis (three-fold increase in transaminases) with nausea and asthenia after one week of treatment, leading to drug discontinuation. [2]
One patient experienced syncope associated with a major QTc interval prolongation to 530 ms (from a baseline of 425 ms) and documented runs of monomorphic VT one month after starting Hydroquinidine. This was considered a possible proarrhythmic event. A QTc >500 ms was observed only in this patient. [2]
Overall, 5 of 35 patients (14%) discontinued Hydroquinidine due to extracardiac side effects (gastrointestinal intolerance or hepatitis). [2]

[1]. Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome. J Am Coll Cardiol. 2017 Dec 19;70(24):3010-3015.

[2]. Hydroquinidine therapy in Brugada syndrome. J Am Coll Cardiol. 2004 May 19;43(10):1853-60.

[3]. Comparison of the effectiveness of dihydroquinidine and quinidine on ventricular ectopy after acute and chronic administration. Cardiovasc Drugs Ther. 1988 Dec;2(5):679-86.

Hydroquinidine is under investigation in clinical trial NCT00927732 (Hydroquinidine Versus Placebo in Patients With Brugada Syndrome).
See also: Hydroquinine (annotation moved to).

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Hydroquinidine is a quinidine derivative used off-label to treat Short QT Syndrome (SQTS), a rare inherited arrhythmogenic disorder characterized by an abnormally short QT interval on the electrocardiogram and a high risk of sudden cardiac death.
The study protocol involved starting Hydroquinidine at a dose of 3 mg/kg/day and gradually titrating upwards to achieve a QTc interval >360 ms. The mean maintenance dose was 584 ± 53 mg/day (approximately 8 mg/kg/day).
The study concludes that long-term treatment with Hydroquinidine is effective in prolonging the QT interval and preventing life-threatening arrhythmic events in high-risk SQTS patients. It suggests the drug could be used as adjunctive therapy to reduce implantable cardioverter-defibrillator (ICD) shocks or as an alternative therapy when an ICD is contraindicated, unavailable, or refused by the patient.
The authors advocate for the continued global availability of quinidine drugs for treating life-threatening inherited arrhythmias like SQTS. [1]
Hydroquinidine chlorhydrate (slow-release preparation) was used in this study for the management of Brugada syndrome (BrS). [2]
The proposed mechanism in BrS is inhibition of the transient outward potassium current (I_to), thereby rebalancing the currents during phase 1 of the epicardial action potential and reducing the substrate for phase 2 re-entry arrhythmias. [2]
The treatment protocol involved an initial EP study. Hydroquinidine was then started, and a repeat EP study was performed after at least two weeks to assess suppression of VT/VF inducibility. Long-term therapy was continued if the patient was non-inducible and tolerated the drug. [2]
Electrocardiographic changes observed with Hydroquinidine included a slight but significant prolongation of QRS duration (by 13 ± 12 ms) and QTc interval (by 10 ± 7 ms). A reduction or normalization of the characteristic Brugada-type ST-segment elevation was observed in 12 of 35 patients (34%), but this was not correlated with prevention of VT/VF inducibility. [2]
The study suggests Hydroquinidine may be an alternative preventive treatment to ICD implantation in selected asymptomatic BrS patients with inducible arrhythmias, but emphasizes the need for careful monitoring of the QTc interval and plasma levels for tolerance and compliance. [2]

C20H26N2O2

326.4326

326.199

1435-55-8

1476-98-8 (mono-hydrochloride);1668-97-9 (mono-hydrochloride)

91503

White to off-white solid powder

1.2±0.1 g/cm3

498.4±30.0 °C at 760 mmHg

169-170 ºC

255.2±24.6 °C

0.0±1.3 mmHg at 25°C

1.626

3.77

45.59

1

4

4

24

432

4

CC[C@H]1CN2CC[C@H]1C[C@@H]2[C@H](C3=C4C=C(C=CC4=NC=C3)OC)O

LJOQGZACKSYWCH-LHHVKLHASA-N

InChI=1S/C20H26N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h4-6,8,11,13-14,19-20,23H,3,7,9-10,12H2,1-2H3/t13-,14-,19+,20-/m0/s1

(S)-[(2R,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： (1). 本产品在运输和储存过程中需避光。  (2). 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~20.83 mg/mL (~63.81 mM)

配方 1 中的溶解度: ≥ 2.08 mg/mL (6.37 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (6.37 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (6.37 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
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10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
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