| CAS |
No.34233-69-7 |
| 中文名称 |
氯氮平N-氧化 |
| 英文名称 |
Clozapine N-oxide |
| 别名 |
氯氮平氮氧化合物;氯氮平N-氧化物 |
| 分子式 |
C18H19ClN4O |
| 分子量 |
342.82 |
| 溶解性 |
Soluble in Water/DMSO |
| 纯度 |
HPLC≥98% |
| 外观(性状) |
Light yellow to yellow Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD00210190 |
| SMILES |
[O-][N+]1(C)CCN(C2=NC3=CC(Cl)=CC=C3NC4=CC=CC=C42)CC1 |
| InChIKey |
OGUCZBIQSYYWEF-UHFFFAOYSA-N |
| InChI |
InChI=1S/C18H19ClN4O/c1-23(24)10-8-22(9-11-23)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)21-18/h2-7,12,20H,8-11H2,1H3 |
| PubChem CID |
135445691 |
| 靶点 |
mAChR; Dopamine Receptor;DREADDs |
| 通路 |
Neuronal Signaling;GPCR & G Protein |
| 背景说明 |
Clozapine N-oxide是氯氮平的代谢产物,可激活DREADDs。 |
| 生物活性 |
Clozapine N-oxide is a major metabolite of Clozapine and a human muscarinic designer receptors (DREADDs) agonist. Clozapine N-oxide activates the DREADD receptor hM3Dq and hM4Di. Clozapine N-oxide can cross the blood-brain barrier[1][2][3][4]. Clozapine is a potent dopamine antagonist and also a potent and selective muscarinic M4 receptor (EC50=11 nM) agonist[5][6]. |
| In Vitro |
Clozapine was studied in functional assays at human muscarinic M1 - M5 receptors expressed in Chinese hamster ovary cells.Clozapine was a full agonist at the muscarinic M4 receptor (EC50 = 11 nM)， producing inhibition of forskolin - stimulated cAMP accumulation. In contrast， clozapine potently antagonized agonist - induced responses at the other four muscarinic receptor subtypes.[6] |
| In Vivo |
Following administration of 10.0 mg/kg CNO， pharmacokinetic analyses replicated recent reports of back - conversion to clozapine in rats and revealed that this phenomenon also occurs in mice.In rats and mice trained to discriminate 1.25 mg/kg clozapine from vehicle， CNO (1.0 - 20.0 mg/kg) produced partial substitution for the clozapine stimulus on average， with full substitution being detected in some individual animals of both species at doses frequently used to activate DREADDs.[2] |
| 数据来源文献 |
[1]. Wess J， et al. Novel designer receptors to probe GPCR signaling and physiology. Trends Pharmacol Sci. 2013 Jul;34(7):385-92.
[2]. Manvich DF， et al. The DREADD agonist clozapine N-oxide (CNO) is reverse-metabolized to clozapine and produces clozapine-like interoceptive stimulus effects in rats and mice. Sci Rep. 2018 Mar 1;8(1):3840.
[3]. van der Peet PL， et al. Gram scale preparation of clozapine N-oxide (CNO)， a synthetic small molecule actuator for muscarinic acetylcholine DREADDs. MethodsX. 2018 Mar 23;5:257-267.
[4]. Joseph Cichon， et al. Branch-specific dendritic Ca(2+) spikes cause persistent synaptic plasticity. Nature. 2015 Apr 9;520(7546):180-5.
[5]. Silva RR， et al. Evaluation of Functional Selectivity of NSC 170973， Clozapine， and LASSBio-579， an Experimental Compound With Antipsychotic-Like Actions in Rodents， at G Protein and Arrestin Signaling Downstream of the Dopamine D2 Receptor. Front Pharmacol. 2019 Jun 4;10:628.
[6]. Zorn SH， et al. Clozapine is a potent and selective muscarinic M4 receptor agonist. Eur J Pharmacol. 1994 Nov 15;269(3):R1-2. |
| 规格 |
2mg 5mg 10mg 25mg 50mg |
| 单位 |
支 |
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