| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
CAS# 224445-12-9. Bis(7)-tacrine dihydrochloride has multiple targets: (1) Acetylcholinesterase (AChE) - it is a dimeric inhibitor derived from tacrine; (2) NMDA receptors (NMDARs) - it blocks NMDA receptors, thereby preventing glutamate‑induced excitotoxicity and neuronal apoptosis; (3) GABAA receptors - it acts as a potent GABAA receptor antagonist. The compound also interacts with the glutamate receptor ionotropic NMDA 2A (NMDAR2A) subunit.
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| ln Vitro |
In vitro, Bis(7)-tacrine dihydrochloride inhibits AChE activity in a concentration‑dependent manner, which increases acetylcholine levels and enhances cholinergic transmission. It blocks NMDA receptors, reducing Ca2+ influx and preventing glutamate‑induced neuronal apoptosis in primary neuronal cultures. As a GABAA receptor antagonist, it reduces GABAergic inhibition, potentially increasing neuronal excitability. These combined mechanisms may contribute to its neuroprotective and cognitive‑enhancing effects. Detailed IC50 values for each target are proprietary or not publicly summarized.
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| ln Vivo |
In vivo, Bis(7)-tacrine dihydrochloride has been studied in animal models of Alzheimer's disease. It improves cognitive function (e.g., in the Morris water maze and passive avoidance tests) and reduces amyloid‑beta pathology and neuroinflammation. The compound is more effective and less hepatotoxic than tacrine, the first FDA‑approved AChE inhibitor for Alzheimer's disease. The dimeric structure also allows for additional interactions at peripheral sites, contributing to its efficacy. In mice, co‑administration with Schisandrol B (Sch B) can further reduce the potential hepatotoxicity of bis(7)-tacrine.
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| Enzyme Assay |
Standard cell‑free AChE inhibition assays can be performed: purified electric eel AChE (0.5-2 U/mL) is incubated with varying concentrations of bis(7)-tacrine (0.01-1000 nM) in 50-100 mM phosphate buffer (pH 8.0) for 10-30 min at 25degC. Ellman's assay is then performed: acetylthiocholine iodide (0.5-1 mM) and DTNB (0.3-0.5 mM) are added, and absorbance at 412 nm is measured for 5-10 min. The IC₅0 is calculated from the inhibition curve. For NMDA receptor binding, rat brain cortical membranes (200 ug protein) are incubated with 5-10 nM [3H]MK-801 in the presence of 10 uM glutamate and 10 uM glycine, plus varying concentrations of bis(7)-tacrine (0.1-1000 nM), in 50 mM Tris‑HCl (pH 7.4) for 60 min at 23degC. Non‑specific binding is determined with 10 uM MK‑801. Bound radioligand is separated by filtration through GF/B filters. The inhibition of specific binding is used to assess NMDA receptor antagonism. For GABAA receptor binding, membranes from rat brain are incubated with 2-5 nM [3H]muscimol and varying concentrations of bis(7)-tacrine in 50 mM Tris‑citrate buffer (pH 7.1) for 30 min at 4degC. Non‑specific binding is determined with 100 uM GABA. Bound radioligand is separated by filtration.
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| Cell Assay |
For cellular neuroprotection assays, primary cortical neurons or SH‑SY5Y cells are seeded in 96‑well plates (40,000 cells/well) in Neurobasal medium or DMEM/F‑12 for 48 h. Cells are pre‑treated with bis(7)-tacrine (0.1-1000 nM) for 24 h, then exposed to glutamate (10-100 uM) for 24 h to induce excitotoxicity. Cell viability is measured by MTT or LDH release. The percentage of neuroprotection is calculated compared to vehicle‑treated controls. For apoptosis assays, cells are stained with annexin V‑FITC/PI and analyzed by flow cytometry. For Western blot analysis, lysates from treated cells are probed for cleaved caspase‑3, cleaved PARP, Bcl‑2, and Bax. For GABAA receptor antagonism, patch‑clamp recordings are performed on cultured hippocampal neurons; bis(7)-tacrine (0.1-10 uM) is applied in the presence of GABA (1-10 uM), and the inhibition of GABA‑evoked currents is measured.
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| Animal Protocol |
In vivo studies are typically performed with male ICR mice (20-30 g) or Sprague‑Dawley rats (200-300 g). Bis(7)-tacrine is formulated in saline or 0.5% methylcellulose and administered orally (1-20 mg/kg) or intraperitoneally (0.5-10 mg/kg) daily for 7-28 days. For Alzheimer's disease models, mice are treated with scopolamine (1-2 mg/kg IP) to induce memory deficits, or with amyloid‑beta (2-5 ug ICV). Bis(7)-tacrine is administered 30-60 min before scopolamine or daily starting 1-3 days before Abeta injection. Cognitive function is assessed using the Morris water maze (latency to platform and probe trial performance) and the passive avoidance test (step‑through latency). At termination, brain homogenates (hippocampus and cortex) are analyzed for AChE activity (Ellman's method), oxidative stress markers (MDA, GSH), and inflammatory cytokines (TNF‑alpha, IL‑1beta). Histological sections are stained with cresyl violet for neuronal morphology. For hepatotoxicity studies, plasma ALT and AST levels are measured. Co‑administration of Schisandrol B (Sch B, 0.125-0.5 mmol/kg) may be included to reduce hepatotoxicity.
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| ADME/Pharmacokinetics |
Bis(7)-tacrine (MW 565.63, C33H42Cl2N4) is a dimeric compound that is moderately lipophilic and can cross the blood‑brain barrier. It is soluble in DMSO. Oral bioavailability is estimated to be moderate (30-50% in rodents). The plasma half‑life is approximately 1-2 hours. It is metabolized in the liver, likely by CYP450 enzymes (CYP1A2, CYP2D6), and excreted in feces and urine. The tetrahydrochloride salt improves water solubility. Detailed pharmacokinetic parameters are not publicly available.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for bis(7)-tacrine are limited. It is less hepatotoxic than tacrine, but liver enzyme elevations (ALT, AST) have been observed at high doses in animal studies. Co‑administration with Schisandrol B (Sch B) can reduce hepatotoxicity. At therapeutic doses (1-5 mg/kg), no significant adverse effects are reported. At higher doses (>20 mg/kg), mild sedation and GI disturbances may occur. No genotoxicity or carcinogenicity data are available. Bis(7)-tacrine dihydrochloride is for research use only, not for human consumption.
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| References |
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| Additional Infomation |
Bis(7)-tacrine dihydrochloride is a dimeric AChE inhibitor derived from tacrine, with additional NMDA receptor antagonist and GABAA receptor antagonist activity. It has been investigated for Alzheimer's disease as a multi‑target compound that enhances cholinergic transmission, reduces excitotoxicity, and modulates GABAergic inhibition. The compound has not entered clinical trials and is not FDA‑approved. Its use is limited to research applications. CAS 224445-12-9. Storage: powder at -20degC for 3 years; in solvent at -80degC for 1 year.
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| Molecular Formula |
C33H42CL2N4
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| Molecular Weight |
565.62
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| Exact Mass |
564.278
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| CAS # |
224445-12-9
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| PubChem CID |
9959612
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
9.765
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
39
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| Complexity |
627
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.Cl.C(CCCNC1=C2CCCCC2=NC2=CC=CC=C12)CCCNC1=C2CCCCC2=NC2=CC=CC=C12
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| InChi Key |
RHKXINFBJWDTSK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C33H40N4.2ClH/c1(2-12-22-34-32-24-14-4-8-18-28(24)36-29-19-9-5-15-25(29)32)3-13-23-35-33-26-16-6-10-20-30(26)37-31-21-11-7-17-27(31)33;;/h4,6,8,10,14,16,18,20H,1-3,5,7,9,11-13,15,17,19,21-23H2,(H,34,36)(H,35,37);2*1H
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| Chemical Name |
N,N'-bis(1,2,3,4-tetrahydroacridin-9-yl)heptane-1,7-diamine;dihydrochloride
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7680 mL | 8.8399 mL | 17.6797 mL | |
| 5 mM | 0.3536 mL | 1.7680 mL | 3.5359 mL | |
| 10 mM | 0.1768 mL | 0.8840 mL | 1.7680 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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