(5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl)-(6-methoxyquinolin-4-yl)methanol;hydron;sulfate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 金鸡纳生物碱
• 英文名称: (5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl)-(6-methoxyquinolin-4-yl)methanol;hydron;sulfate
• 化学式: C40H50N4O8S
• 分子量: 746.9
• InChiKey: RONWGALEIBILOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.17
• 重原子数：
  53
• 可旋转键数：
  8
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  182
• 氢给体数：
  4
• 氢受体数：
  10

ADMET

代谢

奎尼丁在人体内代谢产生2'-羟基奎尼丁。/奎尼丁；来自表格/

QUINIDINE YIELDS 2'-HYDROXYQUINIDINE AS METABOLITE IN MAN. /QUINIDINE; FROM TABLE/

来源:Hazardous Substances Data Bank (HSDB)

代谢

大多数尿液代谢物只在一个位点发生羟基化，要么在喹啉环上，要么在喹诺环上；也可以找到少量二羟基化合物。奎尼丁剂量的代谢部分和代谢途径似乎在患者之间有相当大的差异。

MOST URINARY METABOLITES ARE HYDROXYLATED AT ONLY ONE SITE, EITHER ON THE QUINOLINE RING OR ON THE QUINUCLIDINE RING; SMALL AMOUNTS OF DIHYDROXY COMPOUNDS ARE ALSO FOUND. THE FRACTION OF A DOSE OF QUINIDINE THAT IS METABOLIZED & THE METABOLIC PATHWAY APPEAR TO VARY CONSIDERABLY FROM PATIENT TO PATIENT.

来源:Hazardous Substances Data Bank (HSDB)

代谢

奎尼丁在肝脏中被代谢，主要是通过羟基化反应生成3-羟基奎尼丁和2-喹尼啶酮。这些代谢物可能具有药理活性。大约10-50%的剂量在24小时内以原药形式通过尿液排出（可能是通过肾小球滤过）。/奎尼丁/

Quinidine is metabolized in the liver, principally via hydroxylation to 3-hydroxyquinidine and 2-quinidinone. The metabolites may be pharmacologically active. Approximately 10-50% of a dose is excreted in urine (probably by glomerular filtration) as unchanged drug within 24 hr. /Quinidine/

来源:Hazardous Substances Data Bank (HSDB)

代谢

奎尼丁在人体内代谢产生2'-羟基奎尼丁。/奎尼丁；来自表格/

QUINIDINE YIELDS 2'-HYDROXYQUINIDINE AS METABOLITE IN MAN. /QUINIDINE; FROM TABLE/

来源:Hazardous Substances Data Bank (HSDB)

代谢

大多数尿液代谢物只在一个位点发生羟基化，要么在喹啉环上，要么在喹核啶环上；也有少量发现二羟基化合物。奎尼丁剂量的代谢部分和代谢途径似乎在患者之间有相当大的差异。

MOST URINARY METABOLITES ARE HYDROXYLATED AT ONLY ONE SITE, EITHER ON THE QUINOLINE RING OR ON THE QUINUCLIDINE RING; SMALL AMOUNTS OF DIHYDROXY COMPOUNDS ARE ALSO FOUND. THE FRACTION OF A DOSE OF QUINIDINE THAT IS METABOLIZED & THE METABOLIC PATHWAY APPEAR TO VARY CONSIDERABLY FROM PATIENT TO PATIENT.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

洋地黄糖苷在90%以上的洋地黄化患者中，其血浆浓度会因奎尼丁的服用而增加。变化的程度与奎尼丁的剂量成正比；平均变化约为两倍。奎尼丁的初始效果可能是由于洋地黄从组织结合位点被置换出来。/奎尼丁/

THE ADMIN OF QUINIDINE RESULTS IN AN INCREASE IN THE PLASMA CONCN OF THE GLYCOSIDE IN OVER 90% OF DIGITALIZED PATIENTS. THE DEGREE OF CHANGE IS PROPORTIONAL TO THE DOSE OF QUINIDINE; THE AVERAGE CHANGE IS ABOUT TWO-FOLD. ... THE INITIAL EFFECT OF QUINIDINE MAY BE DUE TO THE DISPLACEMENT OF DIGOXIN FROM BINDING SITES IN TISSUES. /QUINIDINE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

药物...例如苯巴比妥或苯妥英...可能会通过增加消除速率显著缩短奎尼丁的作用持续时间。...硝酸甘油可能会导致服用奎尼丁的患者出现严重的体位性低血压。/奎尼丁/

DRUGS ... SUCH AS PHENOBARBITAL OR PHENYTOIN ... MAY SIGNIFICANTLY SHORTEN DURATION OF ACTION OF QUINIDINE BY INCR RATE OF ELIMINATION. ... NITROGLYCERIN CAN CAUSE SEVERE POSTURAL HYPOTENSION IN PATIENTS WHO ARE TAKING QUINIDINE. /QUINIDINE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

盐酸奎尼丁是一种弱碱，通过肾脏排出...如果尿液的pH值增加，其生物半衰期可能会延长...碳酸酐酶抑制剂、碳酸氢钠和噻嗪类利尿剂，这些都能增加尿液的pH值，可能会增加奎尼丁的脂溶性以及肾小管的再吸收，从而延长其治疗作用。/盐酸奎尼丁/

QUINIDINE IS WEAK BASE EXCRETED ... BY KIDNEY & ITS BIOLOGICAL HALF-LIFE MAY BE PROLONGED ... IF PH OF URINE IS INCREASED. ... CARBONIC ANHYDRASE INHIBITORS, SODIUM BICARBONATE, & THIAZIDE DIURETICS, ALL OF WHICH INCR URINARY PH MAY SERVE TO INCR LIPID SOLUBILITY & TUBULAR REABSORPTION OF QUINIDINE & THUS PROLONG ITS THERAPEUTIC EFFECT. /QUINIDINE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

硫酸奎尼丁（300毫克），缓慢静脉给药，导致由琥珀酰胆碱（40毫克静脉注射）诱导的瘫痪恢复。硫酸奎尼丁可能会增强或导致筒箭毒碱的神经肌肉效应再次出现。/硫酸奎尼丁/

QUINIDINE (300 MG), SLOWLY ADMIN IV, CAUSED RETURN OF PARALYSIS INDUCED BY SUCCINYLCHOLINE (40 MG IV). QUINIDINE MAY ENHANCE OR CAUSE A RECURRENCE OF NEUROMUSCULAR EFFECTS OF TUBOCURARINE. /QUINIDINE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

鉴定：奎尼丁是一种IA类抗心律失常药物。物质来源：奎尼丁是奎宁的D-异构体。奎尼丁是一种生物碱，可以从多种金鸡纳树皮中提取。金鸡纳树皮含有0.25至3.0%的奎尼丁。奎尼丁也可以从奎宁中制备。奎尼丁是一种无味的白色粉末或晶体，具有苦味。硫酸奎尼丁是无色晶体，无味，具有苦味。葡萄糖酸奎尼丁是一种无味的白色粉末。聚半乳糖醛酸奎尼丁是一种粉末。硫酸奎尼丁是一种无味的白色粉末或晶体，具有苦味。 适应症：描述：室性早搏和室性心动过速；室上性心律失常；心房扑动或心房颤动电复律后维持窦性心律。 人体暴露：主要风险和靶器官：心脏毒性是奎尼丁中毒的主要风险。奎尼丁可能诱导中枢神经系统症状。临床效果摘要：毒性效应通常在摄入后2至4小时内出现，但根据奎尼丁盐和制剂形式的不同，潜伏期可能会有所变化。症状可能包括心律失常（尤其是在有基础心血管疾病的患者中）、神经毒性和呼吸抑制。 诊断：心脏干扰：心脏停搏、休克、传导障碍、室性心律失常、心电图改变、神经系统症状：耳鸣、嗜睡、晕厥、昏迷、抽搐、谵妄。呼吸抑制。奎尼丁浓度对于诊断可能有帮助，但对于临床管理没有用处。 禁忌症：对金鸡纳生物碱过敏或特异体质；房室传导阻滞或完全性心脏阻滞；室内传导缺陷；无房性活动；洋地黄中毒；重症肌无力和尖端扭转型室性心律失常。注意事项包括以下内容：充血性心力衰竭、低血压、肾脏疾病、肝衰竭；同时使用其他抗