丙吡胺_用途_密度_熔点_丙吡胺CAS号【3737-09-5】

心脏病类药。抗心律失常，适用于室上性室心早搏、各类心动过速房颤等。

[ 描述 ]:

Disopyramide (Dicorantil) 是一种治疗室性和房性心律失常的 IA 类抗心律失常药物。Disopyramide 阻断心肌快速内向钠电流 (sodium current),延长心肌动作电位持续时间。Disopyramide 抑制 HERG 编码的钾通道 (potassium channels)。Disopyramide 也表现出复杂的蛋白质结合,并具有强大的负性肌力作用。

[ 相关类别 ]:

信号通路 >> 跨膜转运 >> 钠通道

研究领域 >> 心血管疾病

信号通路 >> 跨膜转运 >> 钾通道

[体外研究]

在临床范围内(IC50=7.23μM)二锥体胺的浓度以剂量依赖的方式抑制在-40 mV和+30 mV试验脉冲后记录的HERG尾电流[1]。

[参考文献]

[1]. S V Jones, et al. Non-competitive Effects of Disopyramide at the Neuromuscular Junction: Evidence for Endplate Ion Channel Block. Br J Anaesth. 1987 Jun;59(6):776-83.

[2]. L A Siddoway, et al. Clinical Pharmacokinetics of Disopyramide. Clin Pharmacokinet. May-Jun 1986;11(3):214-22.

[3]. A A Paul, et al. Inhibition of HERG Potassium Channel Current by the Class 1a Antiarrhythmic Agent Disopyramide. Biochem Biophys Res Commun. 2001 Feb 9;280(5):1243-50.

[ 密度 ]:
1.059g/cm3

[ 沸点 ]:
505.2ºC at 760mmHg

[ 熔点 ]:
94.5-950C

[ 分子式 ]:
C₂₁H₂₉N₃O

[ 分子量 ]:
339.47400

[ 闪点 ]:
259.4ºC

[ 精确质量 ]:
339.23100

[ PSA ]:
59.22000

[ LogP ]:
4.06220

[ 储存条件 ]:
2-8°C

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UR8432000

CHEMICAL NAME :: 2-Pyridineacetamide, alpha-(2-(diisopropylamino)ethyl)-alpha-phenyl-

CAS REGISTRY NUMBER :: 3737-09-5

LAST UPDATED :: 199806

DATA ITEMS CITED :: 25

MOLECULAR FORMULA :: C21-H29-N3-O

MOLECULAR WEIGHT :: 339.53

WISWESSER LINE NOTATION :: T6NJ BXR&VZ2NY1&1&Y1&1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 4286 ug/kg

TOXIC EFFECTS :: Cardiac - other changes Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - other changes

REFERENCE :: NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 302,614,1980

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 700 mg/kg/13W-I

TOXIC EFFECTS :: Behavioral - coma Endocrine - hypoglycemia

REFERENCE :: AMDIBO Annales de Medecine Interne. (Masson Abonnements, B.P.22, F-41354 Vineuil Cedex, France) V.120- 1969- Volume(issue)/page/year: 146,209,1995

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 333 mg/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay) Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 38,1398,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 170 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,319,1982

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 800 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 9,829,1978

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 39100 ug/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 :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 352 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 :: 114 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Blood - changes in spleen

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1628,1971

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 305 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,319,1982

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 26 mg/kg

TOXIC EFFECTS :: Behavioral - tremor Behavioral - rigidity (including catalepsy) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4237139

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 36 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - rigidity (including catalepsy) Lungs, Thorax, or Respiration - respiratory depression

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: 136,114,1962

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 42200 ug/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 :: 24900 ug/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 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 14 gm/kg/35D-I

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Cardiac - arrhythmias (including changes in conduction) Related to Chronic Data - death

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,2555,1985

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 11200 mg/kg/4W-C

TOXIC EFFECTS :: Blood - changes in cell count (unspecified) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases Related to Chronic Data - changes in uterine weight

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1628,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 27300 mg/kg/26W-C

TOXIC EFFECTS :: Liver - changes in liver weight Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1628,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 18200 mg/kg/13W-I

TOXIC EFFECTS :: Liver - fatty liver degeneration Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Related to Chronic Data - death

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 27,3536,1993

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 22260 mg/kg/53W-I

TOXIC EFFECTS :: Cardiac - change in rate Gastrointestinal - nausea or vomiting Related to Chronic Data - death

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,2609,1985 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 24 mg/kg

SEX/DURATION :: female 40-41 week(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition

REFERENCE :: AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 162,482,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 11200 mg/kg

SEX/DURATION :: male 28 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1628,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 11200 mg/kg

SEX/DURATION :: female 28 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Maternal Effects - uterus, cervix, vagina

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1628,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 420 mg/kg

SEX/DURATION :: female 9-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1641,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1260 mg/kg

SEX/DURATION :: female 9-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1641,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1260 mg/kg

SEX/DURATION :: female 7-13 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 5,1641,1971 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4710 No. of Facilities: 22 (estimated) No. of Industries: 1 No. of Occupations: 3 No. of Employees: 424 (estimated) No. of Female Employees: 318 (estimated)

[ 符号 ]:

GHS07, GHS08

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302-H361

[ 警示性声明 ]:
P280-P301 + P312 + P330

[ 危害码 (欧洲) ]:
Xn: Harmful;

[ 风险声明 (欧洲) ]:
22

[ 安全声明 (欧洲) ]:
S36

[ 危险品运输编码 ]:
NONH for all modes of transport

[ WGK德国 ]:
3

[ RTECS号 ]:
UR8432000

2-溴吡啶与苄腈、N,N-二异丙基氯乙胺缩合、水解，再与磷酸成盐即得到治疗心律失常药双异丙吡胺。

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