| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
α7 nAChR 10.8 nM (Ki, for rat α7 receptors) α7 nAChR 16.7 nM (Ki, for human α7 receptors) 5-HT3 Receptor 150 nM (Ki)
A-582941 dihydrochloride targets the α7 nicotinic acetylcholine receptor (α7 nAChR) as a partial agonist. It also binds to the human 5-HT3 receptor. By partially activating the α7 nAChR, it modulates cholinergic signaling pathways involved in cognition. Its high affinity (Ki = 10.8 nM in rat brain) and selectivity make it a valuable probe. |
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| ln Vitro |
In PC12 cells, A-582941 (0.1-100 μM) prevents cell death brought on by NGF withdrawal[2]. The number of inhibitory postsynaptic potentials (IPSCs) increases by 260±70%, the sum of amplitudes by 220±30%, and the total of areas by 210±40% when A-582941 (100 nM) is administered[2]. In PC12 cells, A-582941 raises ERK1/2 phosphorylation with an EC50 of 95 nM[2].
In vitro, A-582941 dihydrochloride binds to α7 nAChRs with high affinity, exhibiting Ki values of 10.8 nM (rat) and 16.7 nM (human). It also binds to the human 5-HT3 receptor with a Ki of 150 nM. As a partial agonist, it activates the α7 receptor and its downstream signaling pathways, such as ERK1/2 and CREB phosphorylation, which are involved in cognitive function. |
| ln Vivo |
In freely moving rats, the medial prefrontal cortex (mPFCx) exhibits a moderate increase in ACh release when administered intraperitoneally (3 μM/kg) once daily for three days[2]. A-582941 (0.01-1.00 μM/kg, ip) enhances cAMP response element-binding protein (CREB) phosphorylation in the cingulate cortex of mice and ERK1/2 phosphorylation in the hippocampus in a dose-dependent manner[2]. In the mouse cingulate cortex, A-582941 (0.1-1.0 μM /kg, ip) causes dose-dependent increases in Ser-9 GSK-3β phosphorylation[2]. Following oral dosing (mouse 1.0, rat 6.2, dog 3.0, monkey 3.0 μM/kg), A-582941 has high oral bioavailability (mouse ~100%, rat 90%, dog 22%, monkey 50%) and Cmax (mouse 18, rat 114, dog 79, monkey 39 ng/mL)[2]. Following intravenous administration (mouse 1.0, rat 6.2, dog 0.5, monkey 0.5 μM/kg), A-582941 displays the terminal elimination half-lives (mouse 1.4, rat 1.5, dog 1.4, monkey 2.0 h), plasma clearance (mouse 7.9, rat 4.7, dog 5.3, monkey 1.6 L/h/kg), and volumes of distribution (mouse 11.4, rat 9.2, dog 7.9, monkey 3.9 L/kg).
In vivo, A-582941 dihydrochloride enhances cognitive performance in behavioral models, including tasks that capture working memory, short-term recognition memory, memory consolidation, and sensory gating deficits. It activates signaling pathways (e.g., ERK1/2 and CREB phosphorylation) associated with cognition. In a series of assessments of cardiovascular, gastrointestinal, and central nervous system functions, it demonstrated a favorable secondary pharmacodynamic and tolerability profile. |
| Enzyme Assay |
Non-cell-based assays for A-582941 dihydrochloride include radioligand binding studies to determine its affinity (Ki) for α7 nAChRs and 5-HT3 receptors. Membranes from rat brain or human frontal cortex are incubated with a radiolabeled ligand (e.g., [125I]-α-bungarotoxin for α7 nAChR) and varying concentrations of the compound. The Ki values are calculated from displacement curves.
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| Cell Assay |
For in vitro cellular assays, cells expressing α7 nAChRs are treated with A-582941 dihydrochloride. Its partial agonist activity is confirmed by measuring receptor-mediated signaling. For example, its ability to induce calcium influx or activate downstream kinases like ERK1/2 and CREB can be assessed. The compound's effects are compared to full agonists to confirm its partial agonist profile.
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| Animal Protocol |
Animal/Disease Models: Male SD (Sprague-Dawley) CD rats (250-275 g)[2]
Doses: 3 μM/kg Route of Administration: Ip one time/day for 3 days Experimental Results: Increased the releases of Ach. The effect remained stable after the second and third administration. In vivo animal studies with A-582941 dihydrochloride typically involve administering the compound to rodents (e.g., via intraperitoneal injection). Its effects on cognitive function are then evaluated using behavioral paradigms such as the novel object recognition test or the Morris water maze. The compound's ability to enhance performance in these models supports its potential for treating cognitive deficits. |
| ADME/Pharmacokinetics |
A-582941 dihydrochloride has a molecular weight of 353.29 g/mol and a molecular formula of C17H22Cl2N4. It is a selective and brain-penetrant compound. It is typically supplied as a solid with high purity (e.g., 99.55%). It is soluble in DMSO up to 55 mg/mL and is for research use only.
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| Toxicity/Toxicokinetics |
The toxicity profile of A-582941 dihydrochloride is not fully detailed. However, in a series of safety pharmacology assessments (cardiovascular, gastrointestinal, CNS), it demonstrated a favorable tolerability profile. This suggests it has an acceptable preliminary safety window for use as a research tool. It is not for human consumption.
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| References |
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| Additional Infomation |
A-582941 dihydrochloride (CAS#: 848591-90-2) is a key research tool for studying the role of α7 nAChR in cognition. Its partial agonist activity and brain penetration make it a valuable compound for investigating mechanisms of cognitive enhancement and for developing potential therapeutics for conditions like Alzheimer's disease and schizophrenia.
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| Molecular Formula |
C17H22CL2N4
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|---|---|
| Molecular Weight |
353.29
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| Exact Mass |
280.169
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| CAS # |
848591-90-2
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| PubChem CID |
44190553
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.144
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
21
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| Complexity |
341
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CN1C[C@@H]2CN(C[C@@H]2C1)C3=NN=C(C=C3)C4=CC=CC=C4
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| InChi Key |
GTMRUYCIJSNXGB-GASCZTMLSA-N
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| InChi Code |
InChI=1S/C17H20N4/c1-20-9-14-11-21(12-15(14)10-20)17-8-7-16(18-19-17)13-5-3-2-4-6-13/h2-8,14-15H,9-12H2,1H3/t14-,15+
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| Chemical Name |
(3aR,6aS)-2-methyl-5-(6-phenylpyridazin-3-yl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole
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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. |
| 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) |
DMSO: 100 mg/mL (283.05 mM)
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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 | 2.8305 mL | 14.1527 mL | 28.3054 mL | |
| 5 mM | 0.5661 mL | 2.8305 mL | 5.6611 mL | |
| 10 mM | 0.2831 mL | 1.4153 mL | 2.8305 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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