盐酸可乐定_MSDS_用途_熔点_盐酸可乐定CAS号【4205-91-8】

【用途一】
抗高血压和戒烟戒毒药。

[ 描述 ]:

Clonidine hydrochloride 是 α2-adrenoceptor 激动剂,为一种有效的抗高血压药。

[ 相关类别 ]:

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 肾上腺素能受体

研究领域 >> 心血管疾病

[体外研究]

可乐定(0.01,0.1或1μM)在内皮细胞中以剂量依赖性方式显着诱导CGRP(α和β)mRNA表达。可乐定处理(1μM)24小时显着增加内皮细胞中的NO水平。 NO途径调节可乐定诱导的CGRP产生[2]。

[体内研究]

可乐定(50μg/ kg,ip)诱导持续3小时的大鼠体温的显着降低,在给药后1小时达到最大值。在可乐定15分钟前用中性剂量的酚妥拉明对大鼠进行脑室内预处理可显着拮抗可乐定诱导的低温[1]。可乐定(0.003-0.05mg/kg,ip)有效抑制由PCP诱导的前额皮质中的多巴胺流出。用α-2A受体拮抗剂(BRL-44408)预处理可以阻止可乐定抑制前额皮质中PCP诱导的多巴胺溢出[3]。在DMSO预处理的SO大鼠中,可乐定(0.6μg)对血压没有影响。然而,在SO大鼠中央腺苷A1R阻断(DPCPX)后,可乐定显着(P <0.05,单向ANOVA)降低血压。相比之下,在DMSO预处理的ABD大鼠中,可乐定(0.6μg)导致血压显着降低;重要的是,中枢A1R阻断(DPCPX预处理)不影响(P> 0.05,单向ANOVA)可乐定诱发的ABD大鼠血压降低。在DPCPX预处理的SO大鼠中,伴随着降血压反应的出现,与DMSO预处理的SO大鼠中的基础或可乐定治疗相比,可乐定导致RVLM pERK1/2水平显着(P <0.05)增加。在载体(DMSO)预处理的ABD大鼠中,可乐定显着(P <0.05)增强RVLM pERK1/2,并且该反应不受DPCPX预处理的影响[4]。

[动物实验]

在实验当天，在开始收集基线样品之前约2小时将流速增加至2μL/ min。每20分钟收集一次透析液;在收集4个基线样品后，用腹膜内（ip）注射0.9％盐水（载体），可乐定（0.0033,0.01或0.05mg / kg）或胍法辛（0.05或0.5mg / kg）预处理动物。，在20分钟后接受注射PCP（2.5 mg / kg，ip）之前。在另一项研究中，在可乐定之前20分钟给予BRL（1.0mg / kg）。此外，对于一些对照实验，动物仅接受一次注射盐水，可乐定（0.01或0.05mg / kg），胍法辛（0.5mg / kg）或BRL（1.0mg / kg）。

[参考文献]

[1]. Bugajski J, et al. The involvement of central alpha-adrenergic and histamine H2-receptors in the hypothermia induced by clonidine in the rat. Neuropharmacology. 1980 Jan;19(1):9-15.

[2]. Zhang YM, et al. Clonidine induces calcitonin gene-related peptide expression via nitric oxide pathway in endothelial cells. Peptides. 2009 Sep;30(9):1746-52.

[3]. Jentsch JD, et al. Clonidine and guanfacine attenuate phencyclidine-induced dopamine overflow in rat prefrontal cortex: mediating influence of the alpha-2A adrenoceptor subtype. Brain Res. 2008 Dec 30;1246:41-6.

[4]. Nassar N, et al. Brainstem adenosine A1 receptor signaling masks phosphorylated extracellular signal-regulated kinase 1/2-dependent hypotensive action of clonidine in conscious normotensive rats. J Pharmacol Exp Ther. 2009 Jan;328(1):83-9.

[相关活性小分子]

[ 沸点 ]:
319.3ºC at760mmHg

[ 熔点 ]:
312 °C

[ 分子式 ]:
C₉H₁₀Cl₃N₃

[ 分子量 ]:
266.555

[ 闪点 ]:
146.9ºC

[ 精确质量 ]:
264.994019

[ PSA ]:
36.42000

[ LogP ]:
3.00390

[ 外观性状 ]:
白色到灰白色粉末

[ 储存条件 ]:
2-8°C

[ 水溶解性 ]:
H2O: 50 mg/mL, clear, colorless

详细MSDS(安全技术说明书)

CHEMICAL IDENTIFICATION

RTECS NUMBER :: NJ2490000

CHEMICAL NAME :: 2-Imidazoline, 2-(2,6-dichloroanilino)-, monohydrochloride

CAS REGISTRY NUMBER :: 4205-91-8

LAST UPDATED :: 199504

DATA ITEMS CITED :: 28

MOLECULAR FORMULA :: C9-H9-Cl2-N3.Cl-H

MOLECULAR WEIGHT :: 266.57

WISWESSER LINE NOTATION :: T5M CN BUTJ BMR BG FG &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 180 ug/kg

TOXIC EFFECTS :: Behavioral - coma Cardiac - pulse rate Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983- Volume(issue)/page/year: 7,343,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - infant

DOSE/DURATION :: 390 ug/kg

TOXIC EFFECTS :: Behavioral - coma Cardiac - pulse rate Vascular - BP elevation not characterized in autonomic section

REFERENCE :: PEDIAU Pediatrics. (American Academy of Pediatrics, P.O. Box 1034, Evanston, IL 60204) V.1- 1948- Volume(issue)/page/year: 72,500,1983

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 126 ug/kg/4W-I

TOXIC EFFECTS :: Gastrointestinal - other changes

REFERENCE :: BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 292,174,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 69 ug/kg

TOXIC EFFECTS :: Behavioral - hallucinations, distorted perceptions Vascular - BP lowering not characterized in autonomic section Vascular - pulse pressure increase

REFERENCE :: LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 2,694,1976

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 70 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - other changes

REFERENCE :: AJDCAI American Journal of Diseases of Children. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1-80(3), 1911-50; V.100- 1960- Volume(issue)/page/year: 137,171,1983

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 100 ug/kg

TOXIC EFFECTS :: Behavioral - irritability Cardiac - EKG changes not diagnostic of specified effects Vascular - BP lowering not characterized in autonomic section

REFERENCE :: CTOXAO Clinical Toxicology. (New York, NY) V.1-18, 1968-81. For publisher information, see JTCTDW. Volume(issue)/page/year: 14,271,1979

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 126 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - ataxia Skin and Appendages - hair

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: 18,366,1987

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 91200 ug/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - chromodacryorrhea Behavioral - tremor Behavioral - ataxia

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: 26,4843,1992

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 77 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - ataxia Skin and Appendages - hair

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: 18,366,1987

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 29 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: 16,1038,1966

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 135 mg/kg

TOXIC EFFECTS :: Behavioral - tremor Behavioral - ataxia Skin and Appendages - hair

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: 18,366,1987

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 100 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 :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 59 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - excitement Behavioral - ataxia

REFERENCE :: YKKZAJ Yakugaku Zasshi. Journal of Pharmacy. (Nippon Yakugakkai, 2-12-15 Shibuya, Shibuya-ku, Tokyo 150, Japan) No.1- 1881- Volume(issue)/page/year: 95,966,1975

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 17600 ug/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: 16,1038,1966

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 30 mg/kg

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

REFERENCE :: PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 1,67,1977

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 10 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: 16,1038,1966

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 6 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: 16,1038,1966

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 150 mg/kg

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

REFERENCE :: PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 1,67,1977

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 80 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: 16,1038,1966

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 30 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: 16,1038,1966

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 45 mg/kg

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

REFERENCE :: PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 1,67,1977 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 9100 ug/kg/13W-I

TOXIC EFFECTS :: Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count Blood - changes in leukocyte (WBC) count

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: 26,4843,1992 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 6 mg/kg

SEX/DURATION :: female 30 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes

REFERENCE :: ZPPLBF Zentralblatt fuer Pharmazie, Pharmakotherapie und Laboratoriums-diagnostik. (VEB Verlag Volk und Gesundheit, Neue Gruenstr. 18, 102 Berlin, Ger. Dem. Rep.) V.109- 1970- Volume(issue)/page/year: 114,251,1975

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 5 ug/kg

SEX/DURATION :: female 1 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects Reproductive - Effects on Embryo or Fetus - other effects to embryo

REFERENCE :: ANESAV Anesthesiology. (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1940- Volume(issue)/page/year: 67,A449,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 7500 ng/kg

SEX/DURATION :: female 16 week(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

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: 160,471,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 5 ug/kg

SEX/DURATION :: female 1 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects Reproductive - Effects on Embryo or Fetus - other effects to embryo

REFERENCE :: ANESAV Anesthesiology. (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1940- Volume(issue)/page/year: 67,A448,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 2080 ug/kg

SEX/DURATION :: female 8-20 day(s) after conception

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

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 31,10B,1985 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5327 No. of Facilities: 53 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 859 (estimated) No. of Female Employees: 415 (estimated)

[ 符号 ]:

GHS06

[ 信号词 ]:
Danger

[ 危害声明 ]:
H301-H330

[ 警示性声明 ]:
Missing Phrase - N15.00950417-P260-P304 + P340 + P310-P403 + P233

[ 个人防护装备 ]:
Eyeshields;Faceshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ 危害码 (欧洲) ]:
T+:Verytoxic;

[ 风险声明 (欧洲) ]:
R25;R26

[ 安全声明 (欧洲) ]:
S22-S26-S28-S36/37/39-S45

[ 危险品运输编码 ]:
UN 2811 6.1/PG 1

[ WGK德国 ]:
3

[ RTECS号 ]:
NJ2490000

[ 包装等级 ]:
III

[ 危险类别 ]:
6.1(b)

[ 海关编码 ]:
2933290090

详细合成路线

盐酸可乐定上游产品

盐酸可乐定下游产品

由2,6-二氯苯胺经甲酰化、氯化、环合而得。将所得可乐定与无水乙醇及活性炭一起搅拌，加热回流，滤除活性炭，滤液加入氯化氢乙醇溶液中成盐，冷却结晶，过滤，用无水乙醇洗结晶，干燥，得可乐定盐酸盐。

[ 海关编码 ]: 2933290090

[ 中文概述 ]:
2933290090. 其他结构含非稠合咪唑环的化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%

[ 申报要素 ]: 品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期

[ Summary ]:
2933290090. other compounds containing an unfused imidazole ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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