| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
muscarinic acetylcholine receptors[1]
M2 muscarinic acetylcholine receptor (mAChR). W-84 dibromide is a potent, non-competitive, cationic allosteric modulator that binds to an allosteric site on the M2 receptor. |
|---|---|
| ln Vitro |
The overadditive protective effect of atropine plus W-84 (dibromide) against organophosphate poisoning may be explained by the stabilizing effect of W-84 (dibromide) on antagonist-receptor complexes[1]. W-84 (dibromide) stabilizes antagonist-receptor complexes significantly in addition to inhibiting radioligand association[2].
W-84 dibromide is a potent allosteric modulator of M2-cholinoceptors that retards [3H]N-methylscopolamine dissociation from the receptor. It stabilizes cholinergic antagonist-receptor complexes. The compound exhibits allosteric potency with an EC50 of approximately 1440 nM and a half-life of 18.0 hours in the context of receptor modulation. As a non-competitive antagonist, it does not compete with acetylcholine for the orthosteric binding site but instead modulates receptor function through an allosteric mechanism. It not only inhibits radioligand association but also strongly stabilizes antagonist-receptor complexes. |
| ln Vivo |
In vivo, W-84 dibromide has been shown to be effective in preventing organophosphate intoxication when applied in combination with atropine. This synergistic effect is attributed to its ability to stabilize the antagonist-receptor complex, thereby enhancing the protective effects of atropine against organophosphate poisoning. The compound's ability to stabilize cholinergic antagonist-receptor complexes in vivo contributes to its pharmacological effects.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays are performed to characterize the allosteric modulation of W-84 dibromide at the M2 receptor. Radioligand binding studies using membrane preparations from cells expressing the M2 receptor are conducted. The compound's ability to retard the dissociation of [3H]N-methylscopolamine from the receptor is measured to assess its allosteric effects. The stabilization of antagonist-receptor complexes is evaluated by measuring the rate of radioligand dissociation in the presence and absence of the compound.
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| Cell Assay |
In vitro cell-based assays are conducted using cells expressing recombinant M2 mAChR. The cells are treated with W-84 dibromide, and its effects on receptor function are assessed by measuring its ability to modulate agonist or antagonist binding. The allosteric modulation is characterized by assessing the compound's effects on radioligand association and dissociation kinetics. The selectivity of W-84 dibromide for M2 over other mAChR subtypes is determined by testing its activity at M1, M3, M4, and M5 receptors in parallel assays.
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| Animal Protocol |
In vivo studies are conducted in animal models to evaluate the protective effects of W-84 dibromide against organophosphate poisoning. The compound is administered in combination with atropine to assess its ability to enhance the protective effects of atropine. The efficacy of the combination therapy is evaluated by measuring survival rates and clinical outcomes following organophosphate exposure. The compound's ability to stabilize antagonist-receptor complexes in vivo contributes to its pharmacological effects.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data are publicly available for W-84 dibromide. As a research compound, its ADME properties would be characterized in standard preclinical studies. The compound's ability to reach its target receptors and its duration of action are key parameters for understanding its pharmacological effects. The half-life of 18.0 hours in the context of receptor modulation suggests a relatively long duration of action.
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| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available for W-84 dibromide. As a research chemical, standard safety precautions should be followed. Its toxicity profile is expected to be related to its pharmacological activity as an allosteric modulator of muscarinic receptors, potentially affecting cholinergic signaling in peripheral and central nervous systems.
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| References |
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| Additional Infomation |
Antidote for organophosphate poisoning
W-84 dibromide (HDMPPA) is a potent, non-competitive, cationic allosteric modulator of muscarinic acetylcholine receptors, with selectivity for the M2 receptor subtype. It is used as a research tool to study the allosteric regulation of muscarinic receptors and to understand the structural and functional dynamics of receptor-ligand interactions. The compound has been studied for its potential to prevent organophosphate intoxication when applied in combination with atropine. It is not approved for human therapeutic use and is strictly for research purposes. W-84 dibromide is also known as HDMPPA. |
| Molecular Formula |
C32H44BR2N4O4
|
|---|---|
| Molecular Weight |
708.52
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| Exact Mass |
706.173
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| CAS # |
21093-51-6
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| PubChem CID |
167961
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
42
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| Complexity |
810
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C[N+](C)(CCCCCC[N+](C)(C)CCCN1C(=O)C2=CC=CC=C2C1=O)CCCN3C(=O)C4=CC=CC=C4C3=O.[Br-].[Br-]
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| InChi Key |
DZRJZDQAGMZGGA-UHFFFAOYSA-L
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| InChi Code |
InChI=1S/C32H44N4O4.2BrH/c1-35(2,23-13-19-33-29(37)25-15-7-8-16-26(25)30(33)38)21-11-5-6-12-22-36(3,4)24-14-20-34-31(39)27-17-9-10-18-28(27)32(34)40;;/h7-10,15-18H,5-6,11-14,19-24H2,1-4H3;2*1H/q+2;;/p-2
|
| Chemical Name |
3-(1,3-dioxoisoindol-2-yl)propyl-[6-[3-(1,3-dioxoisoindol-2-yl)propyl-dimethylazaniumyl]hexyl]-dimethylazanium;dibromide
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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: 6.25 mg/mL (8.82 mM)
H2O: 3.03 mg/mL (4.28 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 | 1.4114 mL | 7.0570 mL | 14.1139 mL | |
| 5 mM | 0.2823 mL | 1.4114 mL | 2.8228 mL | |
| 10 mM | 0.1411 mL | 0.7057 mL | 1.4114 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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