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| 靶点 |
muscarinic acetylcholine receptor/mAChR
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| 体外研究 (In Vitro) |
在一项使用转染了人源M4 mAChR的CRISPR-M3 HEK293T细胞进行的CRE-荧光素酶实验中，阿托品抑制了卡巴胆碱(10 μM)诱导的荧光信号，IC50值为390 pM。由此数据计算出的抑制常数(Ki)为140 pM。[3]
在一项使用转染了鸡源M4 mAChR (cM4)的CRISPR-M3 HEK293T细胞进行的CRE-荧光素酶实验中，阿托品抑制了卡巴胆碱(10 μM)诱导的荧光信号，IC50值为710 pM。由此数据计算出的抑制常数(Ki)为120 pM。[3] 在一项使用转染了人源alpha2A-肾上腺素能受体 (hADRA2A)的CRISPR-M3 HEK293T细胞进行的CRE-荧光素酶实验中，阿托品抑制了可乐定(1 μM)诱导的荧光信号，IC50值为45 μM。由此数据计算出的抑制常数(Ki)为14 μM。[3] 研究指出，根据其他文献报道，在高浓度（1-100 μM）下，阿托品对α-肾上腺素能受体也具有拮抗活性。[3] 硫酸阿托品（托品；1 μM；肺静脉和动脉）硫酸盐可抑制乙酰胆碱引起的人体肺静脉扩张[4]。 |
| 体内研究 (In Vivo) |
通常在麻醉期间发生的心律失常可通过硫酸阿托品（托品；10 mg/kg；腹腔注射；40 分钟以上；Peromyscus sp.）抑制[2]。
文章讨论到，局部使用阿托品对儿童近视有效，但1%的剂量会引起副作用。近期研究表明，0.01%浓度的阿托品在保持抑制近视效果的同时，副作用有所减轻。[3] 在鸡的形觉剥夺性近视模型中，已知阿托品可以抑制近视，其在玻璃体中发挥作用的估计浓度范围为0.1-10 mM。[3] 论文引用了研究发现，即消融鸡的胆碱能无长突细胞并不会削弱阿托品对近视的抑制作用，这表明其作用部位可能不在视网膜。[3] 论文还提到，在鸡的视网膜-RPE-脉络膜-巩膜制剂中，使用抑制近视浓度的阿托品处理会导致视网膜神经递质大量、非特异性地释放。[3] 在小鼠巩膜成纤维细胞的体外制备物中，阿托品抑制卡巴胆碱诱导的细胞增殖作用，仅在高浓度（0.5-100 μM）下才能观察到，这比其对mAChRs的Ki值高出了500-1000倍。[3] |
| 酶活实验 |
用于受体拮抗作用的CRE-荧光素酶实验： 将缺乏内源性M3受体的CRISPR-M3 HEK293T细胞，与受体克隆（人源M4、鸡源cM4或人源ADRA2A）、cAMP反应元件荧光素酶载体（CRE-Luc）和海肾荧光素酶对照载体（RLuc）共转染。转染48小时后，将细胞与固定亚最大浓度的激动剂（对于M4/cM4使用10 μM卡巴胆碱，对于ADRA2A使用1 μM可乐定）和递增浓度的待测拮抗剂（包括阿托品）一起孵育4小时。孵育后，裂解细胞，并使用Dual-Glo荧光素酶检测系统依次测量荧光素酶活性。CRE-Luc活性（反映cAMP水平和受体激活）被归一化到RLuc活性（作为细胞活力和转染效率的对照）。通过非线性回归分析归一化数据来确定拮抗剂的IC50值。[3]
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| 细胞实验 |
细胞培养和转染： CRISPR-M3 HEK293T细胞在含10% FBS的DMEM中培养。实验时，将细胞以30%的融合度接种在12孔板中，并使用Lipofectamine LTX进行转染。每个孔，将含有160 ng受体DNA（如人源M4）、180 ng CRE-Luc和160 ng RLuc的Opti-MEM混合物与Lipofectamine LTX溶液混合。室温孵育5分钟后，将复合物加入到细胞中。8小时后更换培养基，转染24小时后，将细胞消化并重新接种到白色底透的96孔板中，密度为每孔7500个细胞。[3]
CRE-荧光素酶发光实验： 在初次转染48小时后，吸去96孔板中的培养基，替换为50 μL含有固定浓度激动剂（M4/cM4用10 μM卡巴胆碱；ADRA2A用1 μM可乐定）和不同浓度拮抗剂（如阿托品）的FluoroBrite DMEM。细胞在37°C孵育4小时。随后，每孔加入50 μL Dual-Glo荧光素酶试剂。振荡孵育10分钟确保细胞裂解后，测量CRE-Luc发光信号。接着，每孔加入50 μL Dual-Glo Stop & Glo试剂，再次振荡孵育10分钟后，测量海肾荧光素酶发光信号。CRE-Luc值通过RLuc值进行归一化，以控制孔间差异。[3] |
| 动物实验 |
The paper discusses animal models and protocols from the perspective of reviewed literature, rather than presenting new in vivo data for atropine. [3]
Chick Model of Myopia: In studies referenced by the paper, form-deprivation myopia (FDM) is induced in chicks. Atropine is administered to inhibit myopia, typically via intravitreal injection. Concentrations used range from 0.1 to 10 mM (estimated vitreal concentration), with a total amount of 20-2000 nmol per injection being common. [3] Rabbit Model for Ocular Distribution: The paper references studies where a single dose of 2% [3H]-atropine was delivered to the conjunctival sac of albino rabbits to study its distribution in ocular tissues. [3] Human Clinical Use: The paper discusses clinical protocols where atropine is delivered as daily eye drops at concentrations ranging from 0.01% to 1% for the treatment of childhood myopia. [3] Animal/Disease Models: White-footed mice (Peromyscus sp.) [2] Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection; once, lasting 40 minutes. Experimental Results: increased heart rate and diminished arrhythmia. |
| 药代性质 (ADME/PK) |
Ocular Distribution (from rabbit studies): One hour after a single topical dose of 2% [3H]-atropine to the conjunctival sac of albino rabbits, the concentration in ocular tissues was 0.09% of the original dose in the sclera, 0.05% in the choroid, and 0.008% in the retina. [3]
Another study cited found 0.01% in the retina and 0.38% in the choroid and sclera 30 minutes after topical application of [C14]-atropine. [3] Estimated Human Ocular Concentrations: Based on the rabbit data, a single topical dose of 0.01% to 1% atropine in humans is estimated to result in concentrations of 0.13-13 μM in the sclera, 0.07-7 μM in the choroid, and 0.01-1.1 μM in the retina. [3] Accumulation and Binding: The paper notes that serum levels of atropine can accumulate with repeated dosing, rising from undetectable levels after a single dose to 1.13-5.23 ng/μL when administered every 4-6 hours over 48 hours. [3] Furthermore, pigmented ocular tissues (RPE, iris, ciliary body, choroid, retina) are particularly adept at retaining atropine, which may lead to a prolonged effect. [3] |
| 毒性/毒理 (Toxicokinetics/TK) |
Clinical Side Effects: At the commonly prescribed 1% concentration for myopia treatment, atropine may induce allergic reactions and mAChR M3-mediated side effects such as mydriasis (pupil dilation), photophobia (light sensitivity), cycloplegia (loss of accommodation), and possibly early presbyopia. [3]
Rebound Effect: Upon cessation of 1% atropine treatment, a "rebound" phenomenon can occur, where myopia progresses at a faster rate than in untreated eyes. This is possibly due to desensitization of target receptors from the high drug concentration. [3] Side Effects at Low Dose: Even with the lower, more favored 0.01% concentration, some patients still complain of complications related to muscarinic receptor blockade, including photophobia and blurred vision. However, these symptoms are typically not severe enough to discontinue treatment. [3] In Vitro Cytotoxicity: In the cell-based assays of this study, high concentrations of atropine did not cause significant cell death in the CRISPR-M3 HEK293T cells, as determined by the Renilla luciferase control. [3] |
| 参考文献 | |
| 其他信息 |
Background: Atropine is a potent, non-selective muscarinic acetylcholine receptor (mAChR) antagonist. It has been the standard pharmacological treatment for myopia, but its mechanism of action in this context is unknown and is a central focus of the research paper. [3]
Mechanism of Action (Proposed): The paper hypothesizes that atropine's anti-myopia effects at the high concentrations used in vivo may be mediated through off-target binding to alpha2A-adrenoceptors (ADRA2A) rather than through its canonical target, the M4 mAChR. This is supported by the correlation between the drug's potency at hADRA2A and its reported ability to inhibit chick FDM, which is not seen for M4/cM4. [3] Clinical Use for Myopia: Topical atropine is effective in controlling myopia progression in children. Due to side effects at higher doses, 0.01% atropine eye drops are currently the most favored concentration prescribed by clinicians in Southeast Asia and North America. [3] Conclusion from the Study: The authors conclude from their data that the action of atropine via the mAChR M4 receptor is highly unlikely to be a factor in myopia control, and that non-mAChR targets, such as alpha-adrenoceptors, warrant further investigation. [3] |
| 分子式 |
2(C17H23NO3).H2SO4
|
|---|---|
| 分子量 |
676.82
|
| 精确质量 |
676.302
|
| 元素分析 |
C, 58.77; H, 7.25; N, 4.03; O, 25.33; S, 4.61
|
| CAS号 |
55-48-1
|
| 相关CAS号 |
Atropine sulfate monohydrate;5908-99-6;Atropine;51-55-8;Atropine hydrobromide;6415-90-3
|
| PubChem CID |
60196398
|
| 外观&性状 |
White to off-white solid powder
|
| 沸点 |
429.8ºC at 760 mmHg
|
| 熔点 |
189-192 °C (A)(lit.)
|
| 闪点 |
213.7ºC
|
| LogP |
4.165
|
| tPSA |
182.52
|
| 氢键供体(HBD)数目 |
4
|
| 氢键受体(HBA)数目 |
12
|
| 可旋转键数目(RBC) |
10
|
| 重原子数目 |
47
|
| 分子复杂度/Complexity |
434
|
| 定义原子立体中心数目 |
4
|
| SMILES |
CN1[C@@H]2CC[C@H]1CC(C2)OC(=O)C(CO)C3=CC=CC=C3.CN1[C@@H]2CC[C@H]1CC(C2)OC(=O)C(CO)C3=CC=CC=C3.OS(=O)(=O)O
|
| InChi Key |
HOBWAPHTEJGALG-JKCMADFCSA-N
|
| InChi Code |
InChI=1S/2C17H23NO3.H2O4S/c2*1-18-13-7-8-14(18)10-15(9-13)21-17(20)16(11-19)12-5-3-2-4-6-12;1-5(2,3)4/h2*2-6,13-16,19H,7-11H2,1H3;(H2,1,2,3,4)/t2*13-,14+,15?,16?;
|
| 化学名 |
[(1S,5R)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate;sulfuric acid
|
| HS Tariff Code |
2934.99.9001
|
| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month 注意： (1). 该产品在溶液状态不稳定，请现配现用。 (2). 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。 |
| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 溶解度 (体外实验) |
H2O : ~100 mg/mL (~295.50 mM)
DMSO : ~62.5 mg/mL (~184.69 mM) |
|---|---|
| 溶解度 (体内实验) |
配方 1 中的溶解度: ≥ 2.08 mg/mL (6.15 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。 *生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。 配方 2 中的溶解度: ≥ 2.08 mg/mL (6.15 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。 例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。 *20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。 View More
配方 3 中的溶解度: ≥ 2.08 mg/mL (6.15 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。 配方 4 中的溶解度: 100 mg/mL (295.50 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶. 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4775 mL | 7.3875 mL | 14.7750 mL | |
| 5 mM | 0.2955 mL | 1.4775 mL | 2.9550 mL | |
| 10 mM | 0.1477 mL | 0.7387 mL | 1.4775 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
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 ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
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