50-54-4

• 常用中文名：硫酸奎尼丁
• 常用英文名：QUINIDINE SULFATE (2:1) (salt)
• CAS号：50-54-4
• 分子式：C₄₀H₅₀N₄O₈S
• 分子量：746.91200
• 相关类别： 原料药 循环系统用药 抗心律失常药
• 发布时间：2018-05-25 08:00:00
• 更新时间：2024-01-02 16:12:27
• 单硫酸奎尼丁是一种抗心律失常剂。单硫酸奎尼丁是一种有效的口服活性选择性细胞色素P450db抑制剂。单硫酸奎尼丁也是一种钾通道阻滞剂,IC50为19.9μM。单硫酸奎尼丁可用于疟疾研究[1][2][3]。

名称

• 中文名: 硫酸奎尼丁
• 英文名: quinidine sulfate
• 中文别名: 硫酸奎尼定

物化性质

• 沸点: 495.9ºC at 760mmHg
• 熔点: 212ºC
• 分子式: C₄₀H₅₀N₄O₈S
• 分子量: 746.91200
• 闪点: 253.7ºC
• 精确质量: 746.33500
• PSA: 174.16000
• LogP: 6.65020

生物活性

• 描述: 单硫酸奎尼丁是一种抗心律失常剂。单硫酸奎尼丁是一种有效的口服活性选择性细胞色素P450db抑制剂。单硫酸奎尼丁也是一种钾通道阻滞剂,IC50为19.9μM。单硫酸奎尼丁可用于疟疾研究[1][2][3]。
• 相关类别:
  研究领域 >> 癌症
  研究领域 >> 心血管疾病
  研究领域 >> 感染
  信号通路 >> 代谢酶/蛋白酶 >> 细胞色素P450
  信号通路 >> 跨膜转运 >> 钾通道
• 体外研究: 奎尼丁是一种影响心肌离子电流的抗心律失常药物,也被证明是多种细胞类型中几类钾通道的有效阻断剂[1]。奎尼丁浴应用导致Ik峰值幅度的剂量依赖性降低。在0 mV时阻断Ik的Kd估计为41μM[1]。奎尼丁引起Ik衰减速率的剂量依赖性增加,这种效应通过膜去极化而增强。奎尼丁还会引起稳态失活曲线的5 mV超极化偏移,并增加失活恢复的半衰期。奎尼丁不影响在-30 mV时测得的失活开始[1]。
• 体内研究: 硫酸奎尼丁被迅速吸收,口服后60-90分钟达到峰值血浆浓度。其他盐(葡萄糖酸盐、聚半乳糖醛酸盐)吸收较慢,峰值浓度较低[2]。奎尼丁约70-90%与血浆蛋白质结合。它经过肝脏氧化代谢形成N-氧化物、3-羟基形式、O-脱甲基形式和2’-奎尼酮。超过一半的开始奎尼丁治疗的患者在治疗的第一年内因副作用而停止。通常包括腹泻、恶心和呕吐,这些不一定与高血浆浓度有关[2]。奎尼丁抑制大鼠体内苯丙胺的代谢。奎尼丁预处理导致对羟基苯丙胺在24小时和48小时的排泄量分别显著减少至溶媒对照水平的7.2%和24.1%,同时苯丙胺的排泄量在24小时到48小时之间显著增加至对照水平的542%[3]。
• 参考文献:

  [1]. Kehl SJ, et al. Quinidine-induced inhibition of the fast transient outward K+ current in rat melanotrophs. Br J Pharmacol. 1991 Jul;103(3):1807-13.

  [2]. Roden DM, et al. Class I antiarrhythmic agents: quinidine, procainamide and N-acetylprocainamide, disopyramide.

  [3]. Moody DE, et al. Quinidine inhibits in vivo metabolism of amphetamine in rats: impact upon correlation between GC/MS and immunoassay findings in rat urine. J Anal Toxicol. 1990 Sep-Oct;14(5):311-7.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : VA5950000 CAS REGISTRY NUMBER : 50-54-4 LAST UPDATED : 199701 DATA ITEMS CITED : 23 MOLECULAR FORMULA : C40-H48-N4-O4.H2-O4-S MOLECULAR WEIGHT : 747.00 WISWESSER LINE NOTATION : T66 BNJ HO1 EYQ- DT66 A B CNTJ G1U1 &WSQQ HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 240 mg/kg/2W-I TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - conjunctive irritation Endocrine - tumors Musculoskeletal - joints REFERENCE : JTCTDW Journal of Toxicology, Clinical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.19- 1982- Volume(issue)/page/year: 20,367,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 272 mg/kg/17D-I TOXIC EFFECTS : Vascular - other changes REFERENCE : AIMDAP Archives of Internal Medicine. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1908- Volume(issue)/page/year: 145,2051,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 386 mg/kg/30D-I TOXIC EFFECTS : Blood - changes in cell count (unspecified) Nutritional and Gross Metabolic - body temperature increase REFERENCE : AJMEAZ American Journal of Medicine. (Technical Pub., 875 Third Ave., New York, NY 10022) V.1- 1946- Volume(issue)/page/year: 77,345,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 9600 mg/kg/8W TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - tremor Lungs, Thorax, or Respiration - other changes REFERENCE : JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 238,884,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 409 gm/kg/14Y TOXIC EFFECTS : Behavioral - hallucinations, distorted perceptions REFERENCE : JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 237,2093,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 88 mg/kg/10D-I TOXIC EFFECTS : Liver - hepatitis (hepatocellular necrosis), diffuse Nutritional and Gross Metabolic - body temperature increase Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases REFERENCE : GASTAB Gastroenterology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1943- Volume(issue)/page/year: 70,1136,1976 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 32 mg/kg/2D TOXIC EFFECTS : Skin and Appendages - dermatitis, irritative (after systemic exposure) REFERENCE : DICPBB Drug Intelligence and Clinical Pharmacy. (POB 42435, Cincinnati, OH 45242) V.3- 1969- Volume(issue)/page/year: 16,615,1982 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Multiple routes SPECIES OBSERVED : Human - man DOSE/DURATION : 30 mg/kg/2D-I TOXIC EFFECTS : Cardiac - arrhythmias (including changes in conduction) Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - cyanosis REFERENCE : AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 16,571,1942 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 456 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 18,1127,1968 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 140 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 1,156,1959 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 610 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 18,1127,1968 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 55 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PJPPAA Polish Journal of Pharmacology and Pharmacy. (ARS Polona, POB 1001, 00-068 Warsaw 1, Poland) V.25- 1973- Volume(issue)/page/year: 44,187,1992 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 505 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FRPPAO Farmaco, Edizione Pratica. (Casella Postale 227, 27100 Pavia, Italy) V.8-43 1953-88 For publisher information, see FRMCE8 Volume(issue)/page/year: 35,49,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 135 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 124,53,1958 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 54 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 105,221,1956 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 19 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - tremor Behavioral - convulsions or effect on seizure threshold REFERENCE : DECRDP Drugs under Experimental and Clinical Research. (Bioscience Ediprint, Blvd. James-Fazy 13, 1201 Geneva 1, Switzerland) V.1- 1977- Volume(issue)/page/year: 10,197,1984 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - cat DOSE/DURATION : 16 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PJPPAA Polish Journal of Pharmacology and Pharmacy. (ARS Polona, POB 1001, 00-068 Warsaw 1, Poland) V.25- 1973- Volume(issue)/page/year: 32,833,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 30 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PJPPAA Polish Journal of Pharmacology and Pharmacy. (ARS Polona, POB 1001, 00-068 Warsaw 1, Poland) V.25- 1973- Volume(issue)/page/year: 32,833,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 362 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FRPPAO Farmaco, Edizione Pratica. (Casella Postale 227, 27100 Pavia, Italy) V.8-43 1953-88 For publisher information, see FRMCE8 Volume(issue)/page/year: 35,49,1980 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 117 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FRPPAO Farmaco, Edizione Pratica. (Casella Postale 227, 27100 Pavia, Italy) V.8-43 1953-88 For publisher information, see FRMCE8 Volume(issue)/page/year: 35,49,1980 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 80504 No. of Facilities: 101 (estimated) No. of Industries: 2 No. of Occupations: 7 No. of Employees: 3397 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 80504 No. of Facilities: 178 (estimated) No. of Industries: 3 No. of Occupations: 6 No. of Employees: 2948 (estimated) No. of Female Employees: 1491 (estimated)

安全

• 危害码 (欧洲): Xn
• 风险声明 (欧洲): 22
• 安全声明 (欧洲): 22-45
• 危险品运输编码: UN 1544