氯氮平作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetClozapineCat. No.: HY-14539CAS No.: 5786-21-0分式: CHClN分量: 326.82作靶點(diǎn): Dopamine Receptor; mAChR作通路: GPCR/G Protein; Neuronal Signaling儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (152.99 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mg

2、Concentration制備儲(chǔ)備液1 mM 3.0598 mL 15.2989 mL 30.5979 mL5 mM 0.6120 mL 3.0598 mL 6.1196 mL10 mM 0.3060 mL 1.5299 mL 3.0598 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro

3、式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (7.65 mM); Clear solution此案可獲得 2.5 mg/mL (7.65 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/m

4、L 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (7.65 mM); Clear solution此案可獲得 2.5 mg/mL (7.65 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄均勻。DMSO 儲(chǔ)備液加到 900 L 20% 的

5、 SBE-CD 理鹽溶液中，混合3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.65 mM); Clear solution此案可獲得 2.5 mg/mL (7.65 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Clozapine (HF 1854) 于治療精神分裂癥的抗精神病藥。氯氮平是多巴胺和許多其他受體的有效拮抗劑，結(jié)合M1受 體

6、的Ki值為 9.5 nM。 Clozapine 也是選擇性的毒蕈堿 M4 受體的激動(dòng)劑 (EC50=11 nM)。IC & Target Ki: 9.5 nM (M1), 51 nM (2-adrenoceptor), 75 nM (D2)1EC50: 11 nM (M4)4體外研究 Clozapine shows the unique property of having antipsychotic action but no Parkinson-like motor side effects. Thechemical structure of clozapine facilitates a

7、 relatively rapid dissociation from D2 receptors. After short-termoccupation of D2 receptors, peak neural activity raises synaptic dopamine, which then displaces clozapine. Whileclozapine also occupies other types of receptors, they may not have a significant role in preventing parkinsonism.Clozapin

8、e is very potent at D2 receptor with a Ki of 75 nM. Clozapine is also potent at the 2-adrenoceptor with a Kivalue of 51 nM1. Clozapine causes paradoxical downregulation of 5-HT2A receptors. Clozapine also binds to 5-HT6and 5-HT7 receptors with high affnity2.體內(nèi)研究 Head-twitch response is decreased and

9、 3Hketanserin binding is downregulated in 1, 7, and 14 days after chronicclozapine. 5-HT2A mRNA is reduced 1 day after chronic clozapine. Induction of c-fos, but not egr-1 and egr-2, isrescued 7 days after chronicclozapine3.PROTOCOLAnimal Mice: Mice are treated chronically (21 days) with 25 mg/kg/da

10、y clozapine. Experiments are conducted 1, 7, 14, and 21Administration 3 days after the last clozapine administration. 3HKetanserin binding and 5-HT2A mRNA expression are determined inmouse somatosensory cortex. Head-twitch behavior, expression of c-fos, which is induced by all 5-HT2A agonists,and ex

11、pression of egr-1 and egr-2, which are LSD-like specific, are assayed3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Seeman P, et al. Clozapine, a fast-off-D2 antipsychotic. ACS Chem Neurosci. 2014 Jan 15;5(1):24-9.2. Zhukovskaya NL, et a

12、l. Clozapine downregulates 5-hydroxytryptamine6 (5-HT6) and upregulates 5-HT7 receptors in HeLa cells. Neurosci Lett. 2000 Jul21;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). 2013Jan;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.Page 2 of 3 www.MedChemEMcePdfHeightCaution: Product has n