CAS號	34233-69-7	產地	國產
規(guī)格	5mg	級別	化工級
證書	ISO系列證書

Clozapine N-oxide (Synonyms: 氯dan平N-氧化物)

Clozapine N-oxide 是一種 Clozapine 的主要代謝產物，也是一種人毒蕈堿設計受體 (DREADDs) 激動劑。Clozapine N-oxide 可ji活 DREADD 受體 hM3Dq 和 hM4Di。Clozapine N-oxide 可以穿過血腦屏障。Clozapine 是一種有效的多巴胺拮抗劑，也一種是有效的選擇性毒蕈堿 M4 受體 (muscarinic M4 receptor) (EC₅₀ 為 11 nM) 激動劑。

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].

IC₅₀ & Target

Human muscarinic designer receptors (DREADDs)^[1]

體外研究(In Vitro)

Clozapine N-oxide (CNO) can bind to non-DREADD receptors at concentrations required for DREADD activation, and undergoes reverse-metabolism to its parent compound clozapine, an atypical antipsychotic that acts at a variety of pharmacological targets and produces numerous physiological and behavioral effects^[2].

體內研究(In Vivo)

After a single intraperitoneal (i.p.) injection of Clozapine N-oxide (1 mg/kg) into mice, Clozapine N-oxide (CNO) plasma levels peak at 15 min and are very low after 2 h. Despite the short plasma half-life of CNO in mice, the biological effects that have been described after acute treatment of DREADD-expressing experimental animals are usually much longer (6-10 h)^[1].

分子量：342.82

Formula：C₁₈H₁₉ClN₄O

CAS 號：34233-69-7

中文名稱：氯dan平N-氧化物

運輸條件：Room temperature in continental US; may vary elsewhere.

儲存方式：

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

溶解性數據

In Vitro:

DMSO : ≥ 100 mg/mL (291.70 mM)

H₂O : 1 mg/mL (2.92 mM; Need ultrasonic)

* "≥" means soluble, but saturation unknown.

配制儲備液

1 mM	2.9170 mL	14.5849 mL	29.1698 mL
5 mM	0.5834 mL	2.9170 mL	5.8340 mL
10 mM	0.2917 mL	1.4585 mL	2.9170 mL

請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。
儲備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 儲存時，請在 6 個月內使用，-20°C 儲存時，請在 1 個月內使用。

In Vivo:

請根據您的實驗動物和給藥方式選擇適當的溶解方案。以下溶解方案都請先按照 In Vitro 方式配制澄清的儲備液，再依次添加助溶劑：

——為保證實驗結果的可靠性，澄清的儲備液可以根據儲存條件，適當保存；體內實驗的工作液，建議您現用現配，當天使用；以下溶劑前顯示的百
分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現沉淀、析出現象，可以通過加熱和/或超聲的方式助溶

1.

請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (7.29 mM); Clear solution
2.

請依序添加每種溶劑： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (7.29 mM); Clear solution
3.

請依序添加每種溶劑： 10% DMSO 90% corn oil
Solubility: ≥ 2.5 mg/mL (7.29 mM); Clear solution
4.

請依序添加每種溶劑： PBS
Solubility: 2.44 mg/mL (7.12 mM); Clear solution; Need ultrasonic and warming and heat to 60°C
5.

請依序添加每種溶劑： 5% DMSO 40% PEG300 5% Tween-80 50% saline
Solubility: ≥ 0.5 mg/mL (1.46 mM); Clear solution
6.

請依序添加每種溶劑： 5% DMSO 95% (20% SBE-β-CD in saline)
Solubility: ≥ 0.5 mg/mL (1.46 mM); Clear solution

參考文獻

[1]. Wess J, et al. Novel designer receptors to probe GPCR signaling and physiology. Trends Pharmacol Sci. 2013 Jul;34(7):385-92. [Content Brief]
[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. [Content Brief]
[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. [Content Brief]
[4]. Joseph Cichon, et al. Branch-specific dendritic Ca(2+) spikes cause persistent synaptic plasticity. Nature. 2015 Apr 9;520(7546):180-5. [Content Brief]
[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 Pharmac [Content Brief]
[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. [Content Brief]

注：產品僅用于科研