Clozapine
(Synonyms: 氯氮平; HF 1854) 目录号 : GC17760
An atypical antipsychotic
Cas No.:5786-21-0
Sample solution is provided at 25 µL, 10mM.
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Clozapine (HF 1854) is an antipsychotic used to treat schizophrenia. Clozapine is a potent antagonist of dopamine and a number of other receptors, with a Ki of 9.5 nM for M1 receptor[1][2][3]. Clozapine is also a potent and selective agonist at the muscarinic M4 receptor (EC50=11 nM)[4].
Clozapine shows the unique property of having antipsychotic action but no Parkinson-like motor side effects. The chemical structure of clozapine facilitates a relatively rapid dissociation from D2 receptors. After short-term occupation of D2 receptors, peak neural activity raises synaptic dopamine, which then displaces clozapine. While clozapine also occupies other types of receptors, they may not have a significant role in preventing parkinsonism. Clozapine is very potent at D2 receptor with a Ki of 75 nM. Clozapine is also potent at the α2-adrenoceptor with a Ki value of 51 nM[1]. Clozapine causes paradoxical downregulation of 5-HT2A receptors. Clozapine also binds to 5-HT6 and 5-HT7 receptors with high affnity[2].
Head-twitch response is decreased and [3H]ketanserin binding is downregulated in 1, 7, and 14 days after chronic clozapine. 5-HT2A mRNA is reduced 1 day after chronic clozapine. Induction of c-fos, but not egr-1 and egr-2, is rescued 7 days after chronicclozapine[3].
References:
[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.
[4]. Zorn SH, et al. Clozapine is a potent and selective muscarinic M4 receptor agonist. Eur J Pharmacol. 1994 Nov 15;269(3):R1-2.
| Cell experiment: | |
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Cell lines |
Prefrontal cortical (PFC) neurons, Rats hepatocytes |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.1-10 μM for 16-72 h; or 20 - 80 μM for 48 h |
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Applications |
Clozapine induced initial pERK1-specific blockade and subsequent activation of the ERK response in prefrontal cortical (PFC) neurons in vitro [1]. Moreover, Clozapine (20-80 μM) concentration-dependently induced hepatotoxicity [2]. |
| Animal experiment: | |
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Animal models |
C57BL/6 mouse model, Male Sprague-Dawley (SD) rats model |
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Dosage form |
1, 2.5 mg/kg; intraperitoneal administration, for 15 h, 24 h; or 25 mg/kg, oral administration, for 7 days |
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Applications |
Clozapine induced ERK1/2 cell signaling activation via the EGF receptor in mouse prefrontal cortex [1]. Moreover, Clozapine treatment led to marked accumulation of triglyceride and increase in gglutamyl transpeptidase (g-GT) activity, liver weight, and serum AST in rats [2]. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1. Pereira, A., Sugiharto-Winarno, A., Zhang, B., Malcolm, P., Fink, G. and Sundram, S. (2012) Clozapine induction of ERK1/2 cell signalling via the EGF receptor in mouse prefrontal cortex and striatum is distinct from other antipsychotic drugs. Int J Neuropsychopharmacol. 15, 1149-1160 2. Jia, L. L., Zhong, Z. Y., Li, F., Ling, Z. L., Chen, Y., Zhao, W. M., Li, Y., Jiang, S. W., Xu, P., Yang, Y., Hu, M. Y., Liu, L. and Liu, X. D. (2014) Aggravation of clozapine-induced hepatotoxicity by glycyrrhetinic acid in rats. J Pharmacol Sci. 124, 468-479 |
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| Cas No. | 5786-21-0 | SDF | |
| 别名 | 氯氮平; HF 1854 | ||
| 化学名 | 3-chloro-6-(4-methylpiperazin-1-yl)-5H-benzo[b][1,4]benzodiazepine | ||
| Canonical SMILES | CN1CCN(CC1)C2=C3C=CC=CC3=NC4=C(N2)C=C(C=C4)Cl | ||
| 分子式 | C18H19ClN4 | 分子量 | 326.82 |
| 溶解度 | ≥ 14.95mg/mL in DMSO | 储存条件 | Store at RT |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0598 mL | 15.2989 mL | 30.5979 mL |
| 5 mM | 0.612 mL | 3.0598 mL | 6.1196 mL |
| 10 mM | 0.306 mL | 1.5299 mL | 3.0598 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet