Amodiaquine dihydrochloride
(Synonyms: 盐酸阿莫地喹,Amodiaquin dihydrochloride) 目录号 : GC60579
A prodrug form of N-desethyl amodiaquine
Cas No.:69-44-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Amodiaquine is a prodrug form of the antimalarial compound N-desethyl amodiaquine .1,2 It is active against several strains of P. falciparum in vitro (EC50s = 0.23-0.52 nM) and exhibits a synergistic effect when used in combination with N-desethyl amodiaquine.1 Amodiaquine dose-dependently inhibits development of parasitemia in a mouse model of P. berghei infection.3
1.Mariga, S.T., Gil, J.P., Sisowath, C., et al.Synergism between amodiaquine and its major metabolite, desethylamodiaquine, against Plasmodium falciparum in vitroAntimicrob. Agents Chemother.48(11)4089-4096(2004) 2.Sá, J.M., Chong, J.L., and Wellems, T.E.Malaria drug resistance: New observations and developmentsEssays Biochem.51137-160(2014) 3.Jacobs, R.L., Alling, D.W., and Cantrell, W.F.An evaluation of antimalarial combinations against Plasmodium berghei in the mouseJ. Parasitol.49(6)920-925(1963)
| Cas No. | 69-44-3 | SDF | |
| 别名 | 盐酸阿莫地喹,Amodiaquin dihydrochloride | ||
| Canonical SMILES | [H]Cl.[H]Cl.OC1=CC=C(NC2=CC=NC3=CC(Cl)=CC=C23)C=C1CN(CC)CC | ||
| 分子式 | C20H24Cl3N3O | 分子量 | 428.78 |
| 溶解度 | DMSO: 125 mg/mL (291.52 mM) | 储存条件 | 4°C, away from moisture and light |
| 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 | 2.3322 mL | 11.661 mL | 23.322 mL |
| 5 mM | 0.4664 mL | 2.3322 mL | 4.6644 mL |
| 10 mM | 0.2332 mL | 1.1661 mL | 2.3322 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。
Solid-State Characterization and Interconversion of Recrystallized Amodiaquine dihydrochloride in Aliphatic Monohydric Alcohols
AAPS PharmSciTech 2016 Apr;17(2):427-35.PMID:26206402DOI:10.1208/s12249-015-0355-4.
Amodiaquine dihydrochloride monohydrate (AQ-DM) was obtained by recrystallizing Amodiaquine dihydrochloride dihydrate (AQ-DD) in methanol, ethanol, and n-propanol. Solid-state characterization of AQ-DD and AQ-DM was performed using X-ray powder diffractometry, Fourier transform infrared spectroscopy, thermogravimetry, and differential scanning calorimetry. All recrystallized samples were identified as AQ-DM. Crystal habits of AQ-DD and AQ-DM were shown to be needle-like and rhombohedral crystals, respectively. When AQ-DD and AQ-DM were exposed to various relative humidity in dynamic vapor sorption apparatus, no solid-state interconversion was observed. However, AQ-DM showed higher solubility than AQ-DD when exposed to bulk water during solubility study, while excess AQ-DM was directly transformed back to a more stable AQ-DD structure. Heating AQ-DM sample to temperatures ≥190°C induced initial change to metastable amorphous form (AQ-DA) which was rapidly recrystallized to AQ-DD upon ≥80%RH moisture exposure. AQ-DD was able to be recrystallized in alcohols (C1-C3) as AQ-DM solid-state structure. In summary, AQ-DM was shown to have different solubility, moisture and temperature stability, and interconversion pathways when compared to AQ-DD. Thus, when AQ-DM was selected for any pharmaceutical applications, these critical transformation and property differences should be observed and closely monitored.
Characterization of stress degradation products of Amodiaquine dihydrochloride by liquid chromatography with high-resolution mass spectrometry and prediction of their properties by using ADMET Predictor™
J Sep Sci 2017 Dec;40(23):4530-4540.PMID:28985017DOI:10.1002/jssc.201700904.
The degradation behavior of Amodiaquine dihydrochloride, an antimalarial drug, was investigated in solution as well as solid states. The drug was subjected to hydrolytic, photolytic, oxidative, and thermal stress conditions, according to International Conference on Harmonization guideline Q1A(R2). It showed extensive hydrolysis in acidic, alkaline, and neutral solutions both with and without light, while it proved to be stable to thermal and oxidative conditions. In total, six degradation products were formed, which were separated on a C8 column, employing a gradient reversed-phase high-performance liquid chromatography method in which acetonitrile and 10 mM ammonium formate (pH 3.0) were used in the mobile phase. To characterize the degradation products, mass fragmentation behavior of the drug was established by direct infusion of solution to quadrupole time-of-flight and multiple-stage mass spectrometry systems. Liquid chromatography with high-resolution mass spectrometry studies were subsequently carried out on the stressed samples using the same gradient high-performance liquid chromatography method employed for the separation of the degradation products. Hydrogen/deuterium exchange studies were additionally conducted to determine the number of labile hydrogen atoms. The degradation pathway of the drug was delineated, justified by mechanistic explanation. Lastly, ADMET Predictor™ software was employed to predict relevant physicochemical and toxicity data for the degradation products.
Intravenous amodiaquine and oral amodiaquine/erythromycin in the treatment of chloroquine-resistant falciparum malaria
Lancet 1985 Oct 12;2(8459):805-8.PMID:2864534DOI:10.1016/s0140-6736(85)90796-2.
In eastern Thailand, 14 adults with moderately severe falciparum malaria were treated with intravenous Amodiaquine dihydrochloride, loading dose 10 mg base/kg infused over 4 h followed by three further intravenous infusions of 5 mg base/kg at 24, 48, and 72 h. All patients were clinically cured--mean fever clearance time 37.8 h (range 24-60), mean parasite clearance time 64.9 h (18-164). There were no serious toxic effects. 33 patients aged over 5 years with uncomplicated falciparum malaria were given oral Amodiaquine dihydrochloride (mean total dose 41 mg base/kg over 3 days) combined with erythromycin estolate (mean dose 48 mg base/kg daily for 5 days). 2 patients failed to respond. In the other 31 patients mean fever clearance time was 55.9 h (range 10-104) and mean parasite clearance time was 65.4 h (40-120). In both studies, more than half the patients followed-up had recurrent parasitaemia but reinfection could not be excluded. Parasites isolated from 18 patients were highly resistant to chloroquine in vitro.
High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain
Cell Stem Cell 2017 Aug 3;21(2):274-283.e5.PMID:28736217DOI:10.1016/j.stem.2017.06.017.
Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and Amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids. Finally, HH and AQ inhibit ZIKV infection in adult mouse brain in vivo. Strikingly, HH suppresses viral propagation when administered to adult mice with active ZIKV infection, highlighting its therapeutic potential. Our approach highlights the power of stem cell-based screens and validation in human forebrain organoids and mouse models in identifying drug candidates for treating ZIKV infection and related neurological complications in fetal and adult patients.
Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex
Pharmacol Res 2023 Mar 21;191:106717.PMID:36948326DOI:10.1016/j.phrs.2023.106717.
Neuroinflammation is tightly associated with onset of depression. The nuclear receptor related 1 protein (Nurr1, also called Nr4a2), its roles in dopaminergic neurons is well understood, which can alleviate inflammation. Nevertheless, potential effects of Nr4a2 on neuroinflammation associated with depression still remains unclear. Chronic lipopolysaccharides (LPS) stress induced depressive-behaviors were confirmed via behavioral tests. Differentially expressed genes were detected by using RNA-sequencing. The anterior cingulate cortex (ACC) tissues were collected for biochemical experiments. The Golgi-Cox staining and virus labeling were used to evaluate the dendritic spines. We applied fluoxetine (FLX) and Amodiaquine dihydrochloride (AQ, a highly selective agonist of Nr4a2) in mice. Overexpression experiments were performed by injecting with AAV-Nr4a2-EGFP into ACC. Chemogenetic activation of CamkII neurons via injecting the hM3Dq virus. Mice treated with LPS displayed depressive- and anxiety-like behaviors. The reduction of Nr4a2 and FosB induced by LPS were rescued by pretreatment with FLX or AQ. More importantly, LPS-induced behavior deficits in mice were also alleviated via fluoxetine treatment and pharmacological activation the expression of Nr4a2. Meanwhile, enhancing the level of Nr4a2 could improve dendritic spines loss of neuron and morphological changes in microglia. Overexpression of Nr4a2 in ACC reversed the depressive- and anxiety-like behaviors caused by LPS administration. Activation of CamkII neurons in ACC could robustly increase the expression of Nr4a2 and improve LPS-induced behavior deficits. Our findings demonstrate that the Nr4a2 may regulate depressive-like behaviors via alleviating the impairment of morphology and function on microglia and CamkII neurons induced by chronic neuroinflammation.