异丙肾上腺素
异丙肾上腺素用途
异丙肾上腺素是一种非选择性的口服活性β-肾上腺素受体激动剂。异丙肾上腺素具有强大的外周血管扩张剂、支气管扩张剂和心脏刺激活性。异丙肾上腺素可用于研究心动过缓和支气管哮喘[1][2][3][4][5][6]。
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异丙肾上腺素名称
[ CAS 号 ]:
7683-59-2
[ 中文名 ]:
异丙肾上腺素
[ 英文名 ]:
Isoproterenol
[中文别名 ]:
[英文别名 ]:
- Isoproterenol
- asiprenol
- asmalar
- Respifral
- isoprel
- Aludrin
- (+/-)-isoproterenol
- A 21
- Aludrine
异丙肾上腺素生物活性
[ 描述 ]:
异丙肾上腺素是一种非选择性的口服活性β-肾上腺素受体激动剂。异丙肾上腺素具有强大的外周血管扩张剂、支气管扩张剂和心脏刺激活性。异丙肾上腺素可用于研究心动过缓和支气管哮喘[1][2][3][4][5][6]。
[ 相关类别 ]:
[体外研究]
异丙肾上腺素(300 nM,3分钟)使完整大鼠脂肪细胞中颗粒cGMP和西洛他胺抑制的低Km cAMP磷酸二酯酶(cAMP PDE)活性增加约100%[1]。异丙肾上腺素抑制大鼠脂肪细胞中胰岛素刺激的葡萄糖转运活性。在不存在腺苷的情况下,异丙肾上腺素促进胰岛素刺激的细胞表面GLUT4可及性的时间依赖性(t1/2约2分钟)降低>50%,这与观察到的转运活性抑制直接相关[2]。异戊二烯(5 nM和10μM)可增加环腺苷酸水平,西洛他胺(10 mM)、环腺苷酸特异性PDE(PDE 4)抑制剂罗利普拉姆(10 mM)和环GMP提升剂(50 nM ANF或30 nM SNP加100 nM DMPPO)可增强这种作用[3]。异丙肾上腺素将Giα-2基因的转录活性提高到对照值的140%,而Gsα的基因特异性杂交保持不变[4]。异丙肾上腺素(20 nM)增加了总iK的振幅,并导致iK激活曲线中约10 mV的负偏移,无论是在300 nM尼索地平的存在下还是在300 nM尼索地平的存在下,以阻断L型Ca2+电流[5]。在兔分离的起搏器细胞中,异戊二烯(20 nM)使窦房结起搏器的自发起搏器率增加16%[5]。
[体内研究]
异戊二烯(口服,0.27-0.64μg/kg)在狗体内通过相对少量的反应被广泛代谢[6]。动物模型：狗[1]剂量：0.27-0.64μg/kg给药：口服结果：尿液中排泄量基本不变,尿液中只有三分之一的放射性以O-甲基代谢物的形式存在。显示血浆放射性几乎完全是共轭异丙肾上腺素,这种代谢物占尿液放射性的80%以上。当血浆浓度较高时,显示的心率恢复到基线值。
异丙肾上腺素物理化学性质
[ 密度 ]:
1.2±0.1 g/cm3
[ 沸点 ]:
417.5±40.0 °C at 760 mmHg
[ 熔点 ]:
165 - 170ºC
[ 分子式 ]:
C11H17NO3
[ 分子量 ]:
211.258
[ 闪点 ]:
179.7±17.9 °C
[ 精确质量 ]:
211.120850
[ PSA ]:
72.72000
[ LogP ]:
0.25
[ 外观性状 ]:
白色结晶粉末
[ 蒸汽压 ]:
0.0±1.0 mmHg at 25°C
[ 折射率 ]:
1.579
[ 储存条件 ]:
2-8 °C， 密封， 干燥
异丙肾上腺素毒性和生态
CHEMICAL IDENTIFICATION
- RTECS NUMBER :
- DO1750000
- CHEMICAL NAME :
- Benzyl alcohol, 3,4-dihydroxy-alpha-((isopropylamino)methyl)-
- CAS REGISTRY NUMBER :
- 7683-59-2
- BEILSTEIN REFERENCE NO. :
- 2213857
- LAST UPDATED :
- 199707
- DATA ITEMS CITED :
- 37
- MOLECULAR FORMULA :
- C11-H17-N-O3
- MOLECULAR WEIGHT :
- 211.29
- WISWESSER LINE NOTATION :
- QR BQ DYQ1MY1&1
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intramuscular
- SPECIES OBSERVED :
- Human
- DOSE/DURATION :
- 14 ug/kg
- TOXIC EFFECTS :
- Cardiac - pulse rate increase, without fall in BP Cardiac - change in rate
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 355 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LDLo - Lowest published lethal dose
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 100 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Subcutaneous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 600 ug/kg
- TOXIC EFFECTS :
- Cardiac - arrhythmias (including changes in conduction)
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 57 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Unreported
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 850 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 450 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 440 mg/kg
- TOXIC EFFECTS :
- Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Sense Organs and Special Senses (Eye) - lacrimation Gastrointestinal - changes in structure or function of salivary glands
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Subcutaneous
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 400 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 83 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- 600 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- 50 mg/kg
- TOXIC EFFECTS :
- Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Sense Organs and Special Senses (Eye) - lacrimation Gastrointestinal - changes in structure or function of salivary glands
- TYPE OF TEST :
- LDLo - Lowest published lethal dose
- ROUTE OF EXPOSURE :
- Unreported
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- 70 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LDLo - Lowest published lethal dose
- ROUTE OF EXPOSURE :
- Unreported
- SPECIES OBSERVED :
- Mammal - cat
- DOSE/DURATION :
- 250 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rabbit
- DOSE/DURATION :
- 3070 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - rabbit
- DOSE/DURATION :
- 27 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LDLo - Lowest published lethal dose
- ROUTE OF EXPOSURE :
- Unreported
- SPECIES OBSERVED :
- Rodent - rabbit
- DOSE/DURATION :
- 250 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - guinea pig
- DOSE/DURATION :
- 270 mg/kg
- TOXIC EFFECTS :
- Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Sense Organs and Special Senses (Eye) - lacrimation Gastrointestinal - changes in structure or function of salivary glands
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Subcutaneous
- SPECIES OBSERVED :
- Rodent - guinea pig
- DOSE/DURATION :
- 320 ug/kg
- TOXIC EFFECTS :
- Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Sense Organs and Special Senses (Eye) - lacrimation Gastrointestinal - changes in structure or function of salivary glands
- TYPE OF TEST :
- LDLo - Lowest published lethal dose
- ROUTE OF EXPOSURE :
- Unreported
- SPECIES OBSERVED :
- Amphibian - frog
- DOSE/DURATION :
- 80 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Subcutaneous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 320 mg/kg/6D-I
- TOXIC EFFECTS :
- Nutritional and Gross Metabolic - weight loss or decreased weight gain
- TYPE OF TEST :
- TCLo - Lowest published toxic concentration
- ROUTE OF EXPOSURE :
- Inhalation
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 250 mg/m3/30M/30D-C
- TOXIC EFFECTS :
- Gastrointestinal - changes in structure or function of salivary glands Endocrine - other changes Related to Chronic Data - death
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 1500 mg/kg/30D-C
- TOXIC EFFECTS :
- Gastrointestinal - changes in structure or function of salivary glands Endocrine - other changes Related to Chronic Data - death
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intraperitoneal
- DOSE :
- 210 mg/kg
- SEX/DURATION :
- male 7 day(s) pre-mating
- TOXIC EFFECTS :
- Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Subcutaneous
- DOSE :
- 750 ug/kg
- SEX/DURATION :
- female 1-19 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intravenous
- DOSE :
- 20 ug/kg
- SEX/DURATION :
- female 20 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intravenous
- DOSE :
- 10 ug/kg
- SEX/DURATION :
- female 8 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Maternal Effects - uterus, cervix, vagina
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Subcutaneous
- DOSE :
- 3 ug/kg
- SEX/DURATION :
- female 8 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Subcutaneous
- DOSE :
- 3 ug/kg
- SEX/DURATION :
- female 8 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - body wall
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Subcutaneous
- DOSE :
- 3 ug/kg
- SEX/DURATION :
- female 8 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - homeostasis
- TYPE OF TEST :
- Unscheduled DNA synthesis
- TYPE OF TEST :
- Mutation test systems - not otherwise specified
- TYPE OF TEST :
- Unscheduled DNA synthesis
- TYPE OF TEST :
- Mutation test systems - not otherwise specified
MUTATION DATA
- TEST SYSTEM :
- Rodent - rat
- DOSE/DURATION :
- 600 mg/kg/10D
- REFERENCE :
- PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 125,722,1967 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 84487 No. of Facilities: 116 (estimated) No. of Industries: 1 No. of Occupations: 3 No. of Employees: 927 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 84487 No. of Facilities: 107 (estimated) No. of Industries: 1 No. of Occupations: 4 No. of Employees: 9570 (estimated) No. of Female Employees: 8201 (estimated)
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异丙肾上腺素制备
儿茶酚经氯乙酰化、胺化、成盐、催化氢化而得。
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