<生产厂家价格>

氯氮平

氯氮平用途

Clozapine (HF 1854) 是用于治疗精神分裂症的抗精神病药。氯氮平是多巴胺和许多其他受体的有效拮抗剂,结合M1受体的Ki值为9.5 nM。

氯氮平名称

[ CAS 号 ]:
5786-21-0

[ 中文名 ]:
氯氮平

[ 英文名 ]:
Clozapine

[中文别名 ]:

[英文别名 ]:

Asaleptin
EINECS 227-313-7
Clorazil
Clozapine
Clozapine (Tautomer)
Iprox
Clozapinum
Azaleptine
Clozaril
Clozapin

氯氮平生物活性

[ 描述 ]:

Clozapine (HF 1854) 是用于治疗精神分裂症的抗精神病药。氯氮平是多巴胺和许多其他受体的有效拮抗剂,结合M1受体的Ki值为9.5 nM。

[ 相关类别 ]:

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 多巴胺受体

信号通路 >> 神经信号通路 >> 多巴胺受体

研究领域 >> 神经疾病

[ 靶点 ]

Ki: 9.5 nM (M1), 51 nM (α2-adrenoceptor), 75 nM (D2)[1]

[体外研究]

氯氮平显示出具有抗精神病作用但不具有帕金森样运动副作用的独特性质。氯氮平的化学结构促进了与D2受体的相对快速的解离。在短期占据D2受体后,峰值神经活动会引起突触多巴胺,然后取代氯氮平。虽然氯氮平也占据其他类型的受体,但它们在预防帕金森病方面可能没有显着作用。氯氮平对D2受体非常有效,Ki为75 nM。氯氮平对α2-肾上腺素能受体也有效,Ki值为51 nM [1]。氯氮平导致5-HT2A受体的反常下调。氯氮平还与高度亲和力的5-HT6和5-HT7受体结合[2]。

[体内研究]

慢性氯氮平后1天,7天和14天,头部抽搐反应降低,[3H]酮色林结合下调。慢性氯氮平后1天,5-HT2A mRNA减少。在慢性氯氮平[3]后7天,拯救c-fos而非egr-1和egr-2的诱导。

[动物实验]

小鼠：用25mg / kg /天氯氮平长期治疗小鼠（21天）。在最后一次氯氮平给药后1,7,14和21天进行实验。 [3H]在小鼠躯体感觉皮层中测定酮色林结合和5-HT2A mRNA表达。测定头痉挛行为，由所有5-HT2A激动剂诱导的c-fos表达，以及LSD样特异性的egr-1和egr-2的表达[3]。

[参考文献]

[1]. Seeman P, et al. Clozapine, a fast-off-D2 antipsychotic. ACS Chem Neurosci. 2014 Jan 15;5(1):24-9.

[2]. Zhukovskaya NL, et al. Clozapine downregulates 5-hydroxytryptamine6 (5-HT6) and upregulates 5-HT7 receptors in HeLa cells. Neurosci Lett. 2000 Jul 21;288(3):236-40.

[3]. Moreno JL, et al. Persistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice. Psychopharmacology (Berl). 2013 Jan;225(1):217-26.

[相关活性小分子]

氯氮平物理化学性质

[ 密度 ]:
1.3±0.1 g/cm3

[ 沸点 ]:
489.2±55.0 °C at 760 mmHg

[ 熔点 ]:
182-185°C

[ 分子式 ]:
C₁₈H₁₉ClN₄

[ 分子量 ]:
326.823

[ 闪点 ]:
249.6±31.5 °C

[ 精确质量 ]:
326.129822

[ PSA ]:
30.87000

[ LogP ]:
2.36

[ 外观性状 ]:
一种黄色,结晶粉末,略可溶于水

[ 蒸汽压 ]:
0.0±1.2 mmHg at 25°C

[ 折射率 ]:
1.681

[ 储存条件 ]:
Store at RT

[ 水溶解性 ]:
ethanol: 1 mg/mL

氯氮平MSDS

详细MSDS(安全技术说明书)

氯氮平毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: HP1750000

CHEMICAL NAME :: 5H-Dibenzo(b,e)(1,4)diazepine, 8-chloro-11-(4-methyl-1-piperazinyl)-

CAS REGISTRY NUMBER :: 5786-21-0

BEILSTEIN REFERENCE NO. :: 0764984

LAST UPDATED :: 199807

DATA ITEMS CITED :: 33

MOLECULAR FORMULA :: C18-H19-Cl-N4

MOLECULAR WEIGHT :: 326.86

WISWESSER LINE NOTATION :: T C676 BM INJ FG J- AT6N DNTJ D1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 3280 mg/kg/82W-I

TOXIC EFFECTS :: Blood - agranulocytosis

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 4762 ug/kg

TOXIC EFFECTS :: Behavioral - ataxia Behavioral - muscle contraction or spasticity Behavioral - antipsychotic

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 5357 ug/kg/5D-I

TOXIC EFFECTS :: Behavioral - hallucinations, distorted perceptions Behavioral - antipsychotic Cardiac - pulse rate increase, without fall in BP

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 429 mg/kg/60D-I

TOXIC EFFECTS :: Behavioral - muscle contraction or spasticity

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 20 mg/kg

TOXIC EFFECTS :: Behavioral - coma Gastrointestinal - changes in structure or function of endocrine pancreas Blood - leukopenia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 280 mg/kg/5W-I

TOXIC EFFECTS :: Liver - hepatitis (hepatocellular necrosis), diffuse Blood - eosinophilia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 27 mg/kg/13D-I

TOXIC EFFECTS :: Autonomic Nervous System - smooth muscle relaxant (mechanism undefined, spasmolytic) Behavioral - hallucinations, distorted perceptions Behavioral - ataxia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 5 mg/kg/7D-I

TOXIC EFFECTS :: Cardiac - pulse rate increase, without fall in BP

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 4286 ug/kg/11D-I

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Blood - changes in cell count (unspecified) Nutritional and Gross Metabolic - body temperature increase

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 28 mg/kg/2W-I

TOXIC EFFECTS :: Gastrointestinal - changes in structure or function of endocrine pancreas

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 2211 mg/kg/37W-I

TOXIC EFFECTS :: Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other Enzymes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 270 mg/kg/6W-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - structural or functional change in trachea or bronchi Gastrointestinal - hypermotility, diarrhea Blood - agranulocytosis

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 251 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 :: 240 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 41600 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory depression

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

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 210 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 :: 150 mg/kg

TOXIC EFFECTS :: Nutritional and Gross Metabolic - body temperature decrease

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 90 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - muscle contraction or spasticity Lungs, Thorax, or Respiration - dyspnea

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 194 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Behavioral - excitement

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 36500 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 145 mg/kg

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 510 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 :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 900 mg/kg/30D-I

TOXIC EFFECTS :: Liver - changes in liver weight Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3650 mg/kg/1Y-I

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Liver - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 6320 mg/kg/52W-I

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Gastrointestinal - changes in structure or function of salivary glands

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 14560 mg/kg/2Y-I

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity) Cardiac - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1080 mg/kg

SEX/DURATION :: female 16-22 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 24 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 96 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - live birth index (measured after birth)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 48 mg/kg

SEX/DURATION :: female 7-12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :: Sex chromosome loss and nondisjunction

MUTATION DATA

TYPE OF TEST :: Cytogenetic analysis

TEST SYSTEM :: Human Lymphocyte

DOSE/DURATION :: 10 mg/L

REFERENCE :: HUGEDQ Human Genetics. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.31- 1976- Volume(issue)/page/year: 38,77,1977 *** REVIEWS *** TOXICOLOGY REVIEW 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: 1,1,1977

氯氮平安全信息

[ 符号 ]:

GHS06, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H301-H341-H361

[ 警示性声明 ]:
Missing Phrase - N15.00950417-P280

[ 危害码 (欧洲) ]:
Xi:Irritant

[ 风险声明 (欧洲) ]:
R22;R36/37/38

[ 安全声明 (欧洲) ]:
S26

[ 危险品运输编码 ]:
UN 2811 6.1/PG 3

[ WGK德国 ]:
3

[ RTECS号 ]:
HP1750000

[ 包装等级 ]:
III

[ 危险类别 ]:
6.1(b)

[ 海关编码 ]:
2933990090

氯氮平合成路线

详细合成路线

氯氮平上下游产品

氯氮平上游产品

氯氮平下游产品

氯氮平制备

2-氨基-4-氯二苯胺-2'-羧酸（4''-甲基）哌嗪与三氯氧磷反应得到氯氮平。

氯氮平海关

[ 海关编码 ]: 2933990090

[ 中文概述 ]:
2933990090. 其他仅含氮杂原子的杂环化合物. 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 ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

氯氮平文献

Characterization of a highly sensitive and selective novel trapping reagent, stable isotope labeled glutathione ethyl ester, for the detection of reactive metabolites.

J. Pharmacol. Toxicol. Methods 76 , 83-95, (2015)

Glutathione (GSH) trapping assays are widely used to predict the post-marketing risk for idiosyncratic drug reactions (IDRs) in the pharmaceutical industry. Although several GSH derivatives have been ...

Antidepressants activate the lysophosphatidic acid receptor LPA(1) to induce insulin-like growth factor-I receptor transactivation, stimulation of ERK1/2 signaling and cell proliferation in CHO-K1 fibroblasts.

Biochem. Pharmacol. 95 , 311-23, (2015)

Different lines of evidence indicate that the lysophosphatidic acid (LPA) receptor LPA1 is involved in neurogenesis, synaptic plasticity and anxiety-related behavior, but little is known on whether th...

Imaging MALDI MS of Dosed Brain Tissues Utilizing an Alternative Analyte Pre-extraction Approach.

J. Am. Soc. Mass Spectrom. 26 , 967-73, (2015)

Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry has been adopted in the pharmaceutical industry as a useful tool to detect xenobiotic distribution within tissues. A uniqu...

更多文献

氯氮平相关知识

氯氮平说明书-氯氮平片的副作用

2019-01-12 19:20:13

导读：氯氮平（Clozapine），为一种非典型抗精神病药物。主要用于治疗其他精神科药物治疗无效的精神分裂症。精神分裂症及分裂情感性障碍用药可能会增加自杀的机会。本品药效较其他典型抗精神病药物为强，因此可用于治疗对于其他药物产生抗性的患者。本品可能会增加发生粒细胞缺乏症的风险，可能会导致死亡。为了...

氯氮平