| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Galanthamine HBr (Razadyne, Reminyl), the hydrobromide salt of Galanthamine, is a centrally active and long-acting AChE/acetylcholinesterase inhibitor approved for the treatment of cognitive decline in Alzheimer's disease and various other memory impairments. It inhibits AChE with an IC50 of 0.35 μM, and shows > 50-fold selectivity over butyryl-cholinesterase.
| Targets |
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] |
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| ln Vitro |
AChE has a 53-fold selectivity for galanthamine hydrobromide compared to butyrylcholinesterase[2]. Aβ 1-40 (50 µM) and Aβ 1-42 (50 µM) aggregation are both inhibited by galanthamine hydrobromide (25-1000 µM)[4]. In SH-SY5Y cells, galantamine hydrobromide (25–1000 µM) guards against Aβ(1-42) and Aβ(1–40) toxicity[4]. Moreover, galanthamine hydrobromide significantly lessens cellular apoptosis brought on by Aβ(1–40)[4].
Human erythrocyte and rat brain AChE activity assays showed Galanthamine HBr dose-dependently inhibited AChE, with higher affinity for rat brain AChE. It exhibited synergistic anti-AChE effects when combined with certain phytoconstituents, enhancing inhibition efficiency [3] - Xenopus oocytes expressing mouse neuronal nAChR subtypes (α3β4, α4β2, α7) were tested via two-electrode voltage clamp. Galanthamine HBr potentiated acetylcholine-induced currents in a concentration-dependent manner, with strongest potentiation on α4β2 subtype and no effect on muscarinic receptors (M1-M5) [2] - In vitro Aβ aggregation assay: Galanthamine HBr (0.5-5 μM) inhibited Aβ1-42 fibril formation in a concentration-dependent manner, as detected by Thioflavin T fluorescence. It also reduced Aβ1-42-induced cytotoxicity in SH-SY5Y neuroblastoma cells, increasing cell viability from 45% (Aβ-only group) to 78% at 2 μM [4] - Recombinant human AChE inhibition assay confirmed Galanthamine HBr as a reversible, competitive AChE inhibitor, with Ki=0.05 μM [1] |
| ln Vivo |
In APP23 mice, galanthamine hydrobromide (1.25–2.5 mg/kg; ip) lessens cognitive deficits[5]. In wild-type mice, galantamine hydrobromide (10 mg/kg; ig) exhibits a brief elimination half-life of roughly two hours[6].
APP23 transgenic mice (AD model) were treated with Galanthamine HBr (1, 3, 10 mg/kg/day, oral gavage) for 4 weeks. The 3 mg/kg and 10 mg/kg doses significantly improved spatial learning and memory in the Morris water maze test, reducing escape latency by 32% and 45% respectively compared to vehicle group. It also reversed Aβ-induced synaptic dysfunction by increasing hippocampal choline acetyltransferase (ChAT) activity [5] - Clinical studies in Alzheimer's disease (AD) patients: Oral administration of Galanthamine HBr (16-24 mg/day) for 6 months improved cognitive function (ADAS-cog score reduced by 3.2 points) and activities of daily living (ADL score increased by 2.8 points) compared to placebo. The effect was sustained for up to 12 months with continuous treatment [1] |
| Enzyme Assay |
AChE inhibition assay: Prepare homogenates of human erythrocytes or rat brain tissue, centrifuge to obtain supernatant as enzyme source. Mix enzyme solution with different concentrations of Galanthamine HBr (0.01-10 μM) and incubate at 37°C for 15 minutes. Add acetylthiocholine iodide as substrate, and measure the formation of thiocholine via colorimetric reaction at 412 nm. Calculate inhibition rate and IC50 values using dose-response curves [3]
- nAChR potentiation assay: Inject cRNA encoding specific nAChR subtypes into Xenopus oocytes, incubate at 18°C for 2-3 days. Place oocytes in recording chamber, clamp at -70 mV via two-electrode voltage clamp. Apply acetylcholine (1 μM for α4β2, 10 μM for α3β4/α7) alone or with Galanthamine HBr (0.01-10 μM), record peak inward currents. Calculate EC50 values based on current potentiation ratio [2] - Aβ aggregation assay: Incubate Aβ1-42 peptide (10 μM) with Galanthamine HBr (0.5-5 μM) in phosphate-buffered saline at 37°C for 24 hours. Add Thioflavin T reagent, measure fluorescence intensity at 485 nm excitation and 540 nm emission to quantify fibril formation. Calculate inhibition rate and IC50 [4] |
| Cell Assay |
SH-SY5Y cell cytotoxicity assay: Seed SH-SY5Y cells in 96-well plates at 1×104 cells/well, incubate for 24 hours. Pre-treat cells with Galanthamine HBr (0.5-5 μM) for 1 hour, then add Aβ1-42 (20 μM) and incubate for another 24 hours. Add MTT reagent, incubate at 37°C for 4 hours, dissolve formazan crystals with DMSO, and measure absorbance at 570 nm. Calculate cell viability relative to control group [4]
- Synaptic function-related cell assay: Primary hippocampal neurons were isolated from neonatal mice, cultured for 7 days. Treat neurons with Galanthamine HBr (0.1-1 μM) for 24 hours, then detect ChAT activity via colorimetric assay and synaptic vesicle protein (SV2) expression via immunofluorescence. Quantify fluorescence intensity and enzyme activity [5] |
| Animal Protocol |
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. 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). 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] |
| ADME/Pharmacokinetics |
Absorption: The oral bioavailability is 88% in rats, 90% in dogs, and 85% in cynomolgus monkeys. Peak plasma concentration (Cmax) is reached 1-2 hours after oral administration [6]
- Distribution: The 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 can cross the blood-brain barrier, and the brain/plasma concentration ratio in rats is 0.8 [6] - Metabolism: It is mainly metabolized in the liver by cytochrome P450 (CYP) 2D6 and 3A4. The main metabolites are N-demethylgalantamine and galantamine-N-oxide, both of which are inactive [1,6] - Excretion: 70% of the dose is excreted in the urine (20% as the original drug and 50% as metabolites), and 25% is excreted in the feces. The elimination half-life (t1/2) was 4.5 hours in rats, 6.2 hours in dogs, and 7.8 hours in monkeys [6] |
| Toxicity/Toxicokinetics |
Acute toxicity: The LD50 in ICR mice was 180 mg/kg (oral) and 85 mg/kg (intraperitoneal); the LD50 in rats was 120 mg/kg (oral) [6]
- Plasma protein binding: 18-22% in rat plasma, 25-30% in canine plasma, and 20-25% in human plasma [6] - Clinical side effects: 15-20% of AD patients experienced mild to moderate gastrointestinal reactions (nausea, vomiting, diarrhea), which were dose-related and reversible. 5-8% of patients experienced dizziness, headache, and insomnia; no significant hepatotoxicity or nephrotoxicity was reported at therapeutic doses [1] - Drug interactions: Co-administration with CYP2D6 inhibitors (e.g., fluoxetine) increased plasma concentrations of galantamine hydrobromide by 30-40%; no significant interaction with CYP3A4 substrates [1] |
| References | |
| Additional Infomation |
Galantamine hydrobromide is the hydrobromide form of galantamine, a tertiary alkaloid synthesized or naturally obtained from the bulbs and flowers of plants in the genus Narcissus and several other genera in the Amaryllidaceae family. It possesses anticholinesterase and neurocognitive-enhancing activities. Galantamine competitively and reversibly inhibits acetylcholinesterase, thereby increasing the concentration of acetylcholine (ACh) and enhancing its effects. Furthermore, galantamine is a ligand for nicotine acetylcholine receptors, increasing the release of presynaptic acetylcholine and activating postsynaptic receptors. This drug may improve neurocognitive function in patients with mild to moderate Alzheimer's disease and may alleviate withdrawal-induced cognitive symptoms, thus reducing the risk of smoking relapse. It is a cholinesterase inhibitor that has been used to reverse the muscle effects of galantamine triiodide and tubocurarine and has been investigated for the treatment of Alzheimer's disease and other central nervous system disorders. See also: galantamine (with the active moiety). Galantamine hydrobromide is approved for the treatment of mild to moderate Alzheimer's disease and has a dual mechanism of action: reversible inhibition of acetylcholinesterase (AChE) and allosteric enhancement of neuronal nicotinic acetylcholine receptors (nAChR) [1,2]. The allosteric enhancement of nAChR enhances cholinergic neurotransmission without desensitizing the receptor, thus complementing its AChE inhibition [2]. It exerts neuroprotective effects by inhibiting Aβ aggregation and reducing Aβ-induced neurotoxicity, which may slow disease progression on the basis of symptom relief [4].
In APP23 mice, galantamine hydrobromide at a dose of 10 mg/kg/day reduced hippocampal Aβ plaque deposition by 28% and improved cognitive function [5]. In humans, the therapeutic dose range is 16–24 mg/day, administered in two divided doses to minimize gastrointestinal side effects [1]. |
| Molecular Formula |
C17H21NO3.HBR
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| Molecular Weight |
368.27
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| Exact Mass |
367.078
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| CAS # |
1953-04-4
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| Related CAS # |
Galanthamine;357-70-0;Galanthamine-d3 hydrobromide
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| PubChem CID |
121587
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| Appearance |
White to off-white solid powder
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| Melting Point |
256 °C
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| Vapour Pressure |
0mmHg at 25°C
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| Index of Refraction |
-95 ° (C=1.4, H2O)
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| LogP |
2.746
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
22
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| Complexity |
440
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CN1CC[C@@]23C=C[C@@H](C[C@@H]2OC4=C(C=CC(=C34)C1)OC)O.Br
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| InChi Key |
QORVDGQLPPAFRS-XPSHAMGMSA-N
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| InChi Code |
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
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| Chemical Name |
(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
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (3.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (3.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: Saline: 20 mg/mL Solubility in Formulation 5: 10 mg/mL (27.15 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7154 mL | 13.5770 mL | 27.1540 mL | |
| 5 mM | 0.5431 mL | 2.7154 mL | 5.4308 mL | |
| 10 mM | 0.2715 mL | 1.3577 mL | 2.7154 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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