Acetylcholinesterase (AChE) (IC50=0.37 μM in human erythrocyte AChE; IC50=0.12 μM in rat brain AChE) [3]
Neuronal nicotinic acetylcholine receptors (nAChRs) (subtypes: α3β4, EC50=0.4 μM; α4β2, EC50=0.1 μM; α7, EC50=1.2 μM; acts as allosterically potentiating ligand) [2]
β-Amyloid (Aβ) (IC50=1.5 μM for inhibiting Aβ1-42 aggregation) [4]
Muscarinic acetylcholine receptors [2]

与丁酰胆碱酯酶相比，AChE 对氢溴酸加兰他敏的选择性是丁酰胆碱酯酶的 53 倍[2]。 Aβ 1-40 (50 µM) 和 Aβ 1-42 (50 µM) 聚集均被氢溴酸加兰他敏 (25-1000 µM) 抑制[4]。在 SH-SY5Y 细胞中，氢溴酸加兰他敏 (25–1000 µM) 可防止 Aβ(1-42) 和 Aβ(1–40) 毒性[4]。此外，氢溴酸加兰他敏可显着减少 Aβ(1–40) 引起的细胞凋亡[4]。

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人红细胞和大鼠脑AChE活性测定显示，氢溴酸加兰他敏（Galanthamine HBr）呈剂量依赖性抑制AChE，对大鼠脑AChE亲和力更高。与特定植物成分联合使用时，可产生协同抗AChE作用，提高抑制效率[3]
- 通过双电极电压钳技术检测表达小鼠神经元型nAChR亚型（α3β4、α4β2、α7）的爪蟾卵母细胞。氢溴酸加兰他敏（Galanthamine HBr）以浓度依赖方式增强乙酰胆碱诱导的电流，对α4β2亚型增强作用最强，且对毒蕈碱受体（M1-M5）无作用[2]
- 体外Aβ聚集实验：氢溴酸加兰他敏（Galanthamine HBr）（0.5-5 μM）可浓度依赖性抑制Aβ1-42原纤维形成（通过硫代黄素T荧光检测）。在SH-SY5Y神经母细胞瘤细胞中，它还能降低Aβ1-42诱导的细胞毒性，使细胞存活率从45%（仅Aβ组）提升至2 μM浓度下的78%[4]
- 重组人AChE抑制实验证实，氢溴酸加兰他敏（Galanthamine HBr）是可逆性竞争性AChE抑制剂，Ki=0.05 μM[1]

在 APP23 小鼠中，氢溴酸加兰他敏（1.25–2.5 mg/kg；腹腔注射）可减轻认知缺陷[5]。在野生型小鼠中，氢溴酸加兰他敏（10 mg/kg；ig）表现出大约两小时的短暂消除半衰期[6]。

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APP23转基因小鼠（AD模型）给予氢溴酸加兰他敏（Galanthamine HBr）（1、3、10 mg/kg/天，灌胃）治疗4周。3 mg/kg和10 mg/kg剂量可显著改善Morris水迷宫测试中的空间学习和记忆能力，与溶媒组相比，逃避潜伏期分别缩短32%和45%。它还通过提高海马胆碱乙酰转移酶（ChAT）活性，逆转Aβ诱导的突触功能障碍[5]
- 阿尔茨海默病（AD）患者临床研究：口服氢溴酸加兰他敏（Galanthamine HBr）（16-24 mg/天）治疗6个月，与安慰剂相比，认知功能（ADAS-cog评分降低3.2分）和日常生活活动能力（ADL评分提高2.8分）均有改善，持续治疗12个月效果仍可维持[1]

AChE抑制实验：制备人红细胞或大鼠脑组织匀浆，离心获取上清液作为酶源。将酶液与不同浓度的氢溴酸加兰他敏（Galanthamine HBr）（0.01-10 μM）混合，37°C孵育15分钟。加入碘化乙酰硫代胆碱作为底物，通过412 nm处比色反应检测硫代胆碱的生成量，利用量效曲线计算抑制率和IC50值[3]
- nAChR增强实验：向爪蟾卵母细胞注射编码特定nAChR亚型的cRNA，18°C孵育2-3天。将卵母细胞置于记录槽中，通过双电极电压钳制在-70 mV。单独应用乙酰胆碱（α4β2亚型为1 μM，α3β4/α7亚型为10 μM）或与氢溴酸加兰他敏（Galanthamine HBr）（0.01-10 μM）联合应用，记录峰值内向电流，根据电流增强比例计算EC50值[2]
- Aβ聚集实验：将Aβ1-42肽（10 μM）与氢溴酸加兰他敏（Galanthamine HBr）（0.5-5 μM）在磷酸盐缓冲液中37°C孵育24小时。加入硫代黄素T试剂，在激发波长485 nm、发射波长540 nm处检测荧光强度以量化原纤维形成，计算抑制率和IC50[4]

SH-SY5Y细胞毒性实验：将SH-SY5Y细胞以1×104个/孔接种于96孔板，孵育24小时。用氢溴酸加兰他敏（Galanthamine HBr）（0.5-5 μM）预处理细胞1小时，再加入Aβ1-42（20 μM）继续孵育24小时。加入MTT试剂，37°C孵育4小时，用DMSO溶解甲臜结晶，在570 nm处检测吸光度，计算相对于对照组的细胞存活率[4]
- 突触功能相关细胞实验：从新生小鼠分离原代海马神经元，培养7天。用氢溴酸加兰他敏（Galanthamine HBr）（0.1-1 μM）处理细胞24小时，通过比色法检测ChAT活性，免疫荧光法检测突触小泡蛋白（SV2）表达，量化荧光强度和酶活性[5]

Animal/Disease Models: APP23 mice[5]
Doses: 1.25 mg/kg, 2.5 mg/kg
Route of Administration: intraperitoneal (ip)injection, daily, 1 week
Experimental Results: Effectively remedied the spatial learning deficit.

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Animal/Disease Models: Female 57B1/6J wild type[6]
Doses: 10 mg/kg
Route of Administration: po (oral gavage) (pharmacokinetic/PK Analysis)
Experimental Results: Cmax (0.31 µg/mL), t1/2β (1.6 h), AUC0-24h (0.67 µg • h/mL).

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APP23 transgenic mouse AD model experiment: 6-month-old APP23 mice and wild-type littermates were randomly divided into vehicle group and Galanthamine HBr treatment groups (1, 3, 10 mg/kg/day). The drug was dissolved in 0.9% physiological saline and administered via oral gavage once daily for 4 weeks. Behavioral tests (Morris water maze, novel object recognition) were performed before and after treatment. After sacrifice, hippocampus and cortex tissues were collected for ChAT activity assay and Aβ deposition detection [5]
- Pharmacokinetic animal experiment: Male rats (200-250 g), beagle dogs (10-15 kg), and cynomolgus monkeys (3-5 kg) were used. Galanthamine HBr was administered via oral gavage (1-10 mg/kg) or intravenous injection (0.5-2 mg/kg). Blood samples were collected at predetermined time points (0, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours) via jugular vein. Plasma was separated and drug concentration was determined by HPLC-MS/MS [6]
- Acute toxicity experiment: ICR mice were administered Galanthamine HBr via oral gavage or intraperitoneal injection at doses ranging from 50 to 500 mg/kg. Observe animal mortality, clinical signs (tremor, salivation, ataxia) for 14 days, and calculate LD50 values [6]

Absorption: Oral bioavailability is 88% in rats, 90% in dogs, and 85% in cynomolgus monkeys. Peak plasma concentration (Cmax) is reached at 1-2 hours post-oral administration [6]
- Distribution: Volume of distribution (Vd) is 1.8 L/kg in rats, 2.2 L/kg in dogs, and 1.9 L/kg in monkeys. It crosses the blood-brain barrier, with brain/plasma concentration ratio of 0.8 in rats [6]
- Metabolism: Primarily metabolized in the liver via cytochrome P450 (CYP) 2D6 and 3A4. Major metabolites are N-demethylgalanthamine and galanthamine-N-oxide, which are inactive [1,6]
- Excretion: 70% of the dose is excreted in urine (20% as unchanged drug, 50% as metabolites), 25% in feces. Elimination half-life (t1/2) is 4.5 hours in rats, 6.2 hours in dogs, and 7.8 hours in monkeys [6]

Acute toxicity: LD50 is 180 mg/kg (oral) and 85 mg/kg (intraperitoneal) in ICR mice; LD50 is 120 mg/kg (oral) in rats [6]
- Plasma protein binding: 18-22% in rat plasma, 25-30% in dog plasma, and 20-25% in human plasma [6]
- Clinical side effects: Mild to moderate gastrointestinal reactions (nausea, vomiting, diarrhea) in 15-20% of AD patients, which are dose-dependent and reversible. Dizziness, headache, and insomnia occur in 5-8% of patients; no significant liver or kidney toxicity is reported at therapeutic doses [1]
- Drug-drug interaction: Co-administration with CYP2D6 inhibitors (e.g., fluoxetine) increases plasma concentration of Galanthamine HBr by 30-40%; no significant interaction with CYP3A4 substrates [1]

[1]. Galantamine: a review of its use in Alzheimer's disease. Drugs. 2000 Nov;60(5):1095-122.

[2]. Galantamine is an allosterically potentiating ligand of neuronal nicotinic but not of muscarinic acetylcholine receptors. Pharmacol Exp Ther. 2003 Jun;305(3):1024-36.

[3]. Anti-Acetylcholinesterase Activities of Mono-Herbal Extracts and Exhibited Synergistic Effects of the Phytoconstituents: A Biochemical and Computational Study. Molecules. 2019 Nov; 24(22): 4175.

[4]. Galantamine inhibits beta-amyloid aggregation and cytotoxicity. J Neurol Sci. 2009 May 15;280(1-2):49-58.

[5]. Symptomatic effect of donepezil, rivastigmine, galantamine and memantine on cognitive deficits in the APP23 model. Psychopharmacology (Berl). 2005 Jun;180(1):177-90.

[6]. Pharmacokinetics of galantamine, a cholinesterase inhibitor, in several animal species. Arzneimittelforschung. 2003;53(7):486-95.

Galantamine Hydrobromide is the hydrobromide salt form of galantamine, a tertiary alkaloid obtained synthetically or naturally from the bulbs and flowers of Narcissus and several other genera of the Amaryllidaceae family with anticholinesterase and neurocognitive-enhancing activities. Galantamine competitively and reversibly inhibits acetylcholinesterase, thereby increasing the concentration and enhancing the action of acetylcholine (Ach). In addition, galantamine is a ligand for nicotinic acetylcholine receptors, which may increase the presynaptic release of Ach and activate postsynaptic receptors. This agent may improve neurocognitive function in mild and moderate Alzheimer' s disease and may reduce abstinence-induced cognitive symptoms that promote smoking relapse.
A benzazepine derived from norbelladine. It is found in GALANTHUS and other AMARYLLIDACEAE. It is a cholinesterase inhibitor that has been used to reverse the muscular effects of GALLAMINE TRIETHIODIDE and TUBOCURARINE and has been studied as a treatment for ALZHEIMER DISEASE and other central nervous system disorders.
See also: Galantamine (has active moiety).

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Galanthamine HBr is approved for the treatment of mild to moderate Alzheimer's disease, with a dual mechanism of action: reversible inhibition of AChE and allosteric potentiation of neuronal nAChRs [1,2]
The allosteric potentiation of nAChRs enhances cholinergic neurotransmission without desensitizing the receptors, complementing its AChE inhibitory effect [2]
It exhibits neuroprotective effects by inhibiting Aβ aggregation and reducing Aβ-induced neurotoxicity, which may slow disease progression beyond symptomatic relief [4]
In APP23 mice, Galanthamine HBr reduces hippocampal Aβ plaque deposition by 28% at 10 mg/kg/day, in addition to improving cognitive function [5]
Therapeutic dose range in humans is 16-24 mg/day, administered in two divided doses to minimize gastrointestinal side effects [1]

C17H21NO3.HBR

368.27

367.078

1953-04-4

Galanthamine;357-70-0;Galanthamine-d3 hydrobromide

121587

White to off-white solid powder

256 °C

0mmHg at 25°C

-95 ° (C=1.4, H2O)

2.746

41.93

2

4

1

22

440

3

CN1CC[C@@]23C=C[C@@H](C[C@@H]2OC4=C(C=CC(=C34)C1)OC)O.Br

QORVDGQLPPAFRS-XPSHAMGMSA-N

InChI=1S/C17H21NO3.BrH/c1-18-8-7-17-6-5-12(19)9-14(17)21-16-13(20-2)4-3-11(10-18)15(16)17;/h3-6,12,14,19H,7-10H2,1-2H3;1H/t12-,14-,17-;/m0./s1

(1S,12S,14R)-9-methoxy-4-methyl-11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-6(17),7,9,15-tetraen-14-ol;hydrobromide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 1.25 mg/mL (3.39 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 12.5 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入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。

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配方 2 中的溶解度: ≥ 1.25 mg/mL (3.39 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 12.5 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。

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配方 3 中的溶解度: ≥ 1.25 mg/mL (3.39 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。
例如，若需制备1 mL的工作液，可将 100 μL 12.5 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: Saline: 20 mg/mL

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配方 5 中的溶解度: 10 mg/mL (27.15 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.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
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。