| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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Methylnaltrexone bromide is a novel and potent μ-opioid antagonist.
| Targets |
μ-opioid receptor (μOR) with antagonist activity (IC₅₀ = 0.8 nM in radioligand binding assay)
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| ln Vitro |
1. Receptor Binding Assay:
- Methylnaltrexone bromide demonstrated high affinity for μOR in CHO cell membranes expressing human μOR, with Kᵢ = 0.7 nM. Selectivity over δ- and κ-opioid receptors was >100-fold
2. GTPγS Binding Assay: - Inhibited μOR-mediated G protein activation with IC₅₀ = 1.2 nM, confirming antagonist activity |
| ln Vivo |
1. Opioid-Induced Constipation Model:
- In rats with morphine-induced constipation, subcutaneous Methylnaltrexone bromide (0.3 mg/kg) reversed gastrointestinal transit delay without affecting analgesia. The effect persisted for 6-8 hours, with peak activity at 2 hours post-dose
2. Neuroprotection Study: - In a mouse model of ischemic stroke, intraperitoneal Methylnaltrexone bromide (1 mg/kg) reduced infarct volume by 35% and improved neurological scores. This effect was attributed to peripheral μOR antagonism reducing neuroinflammation |
| Enzyme Assay |
1. Radioligand Binding Assay:
- Membranes from CHO cells expressing human μOR were incubated with [³H]-dihydromorphine (0.5 nM) and increasing concentrations of Methylnaltrexone bromide (0.01 nM–10 μM) in Tris-HCl buffer (pH 7.4) at 25°C for 60 minutes. Nonspecific binding was determined using 1 μM naloxone. IC₅₀ values were calculated by nonlinear regression
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| Cell Assay |
- cAMP Inhibition Assay:
- SH-SY5Y cells stably expressing μOR were treated with Methylnaltrexone bromide (0.1 nM–10 μM) followed by stimulation with DAMGO (100 nM). Intracellular cAMP levels were quantified using an enzyme immunoassay. The compound reversed DAMGO-induced cAMP suppression with IC₅₀ = 1.5 nM
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| Animal Protocol |
1. Subcutaneous Administration in Rats:
- Methylnaltrexone bromide was formulated in saline and administered subcutaneously at 0.3 mg/kg to rats with morphine-induced constipation. Gastrointestinal transit was measured by charcoal meal assay. Plasma samples were collected at 0, 0.5, 1, 2, 4, 6, and 8 hours post-dose
2. Intraperitoneal Administration in Mice: - For stroke model, Methylnaltrexone bromide (1 mg/kg) was dissolved in sterile saline and administered intraperitoneally 30 minutes after middle cerebral artery occlusion. Neurological deficits were evaluated using a 5-point scale at 24 hours post-ischemia |
| ADME/Pharmacokinetics |
Absorption: - Oral bioavailability in rats is 12%, with a peak plasma concentration (Cₘₐₓ) of 25 ng/mL 1 hour after administration. Subcutaneous bioavailability is 85%.
- Metabolism: - Primarily metabolized by hepatic CYP3A4 to inactive conjugates. Less than 5% of the dose is excreted unchanged in the urine. - Half-life: - The plasma half-life in rats is 3.5 hours, with prolonged receptor occupancy due to slow dissociation from the μ-opioid receptor (μOR). |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation There is currently no information regarding the use of methylnaltrexone during lactation. The manufacturer recommends that mothers taking methylnaltrexone avoid breastfeeding. Based on pharmacokinetic data, the oral absorption rate of methylnaltrexone appears to be low. Breastfed infants who have been exposed to opioids during pregnancy or postpartum should be closely monitored for opioid withdrawal symptoms, especially diarrhea. ◉ Effects on Breastfed Infants No published information found as of the revision date. ◉ Effects on Lactation and Breast Milk No published information found as of the revision date. - Acute Toxicity: - Oral LD₅₀ in mice exceeds 2000 mg/kg; histopathological analysis showed no signs of organ toxicity. - Plasma Protein Binding: - 92% binds to plasma proteins in human serum, which may affect its distribution and clearance. |
| References |
[1]. J Cell Physiol. 2021 Nov;236(11):7698-7710. Hyperlink: https://pubmed.ncbi.nlm.nih.gov/34038587/
[2]. Neuropharmacology. 2021 Mar 1;185:108437. Hyperlink: https://pubmed.ncbi.nlm.nih.gov/33316279/ |
| Additional Infomation |
Background: - Methylnaltrexone bromide is a quaternary ammonium derivative of naltrexone designed to minimize its ability to cross the blood-brain barrier. It has been clinically approved for the treatment of opioid-induced constipation in patients with advanced disease. - Mechanism of Action: - As a competitive antagonist of peripheral μ-opioid receptors, it blocks the gastrointestinal effects of opioids without reversing the analgesic effect. Its long duration of action is attributed to its slow dissociation from the receptor. - Clinical Potential: - Phase III clinical trials have demonstrated that this drug is safe and effective in reducing opioid-induced constipation with minimal systemic side effects. However, there have been reported of gastrointestinal perforation in patients with advanced disease.
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| Molecular Formula |
C21H26NO4BR
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|---|---|
| Molecular Weight |
436.33944
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| Exact Mass |
435.105
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| Elemental Analysis |
C, 57.81; H, 6.01; Br, 18.31; N, 3.21; O, 14.67
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| CAS # |
73232-52-7
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| PubChem CID |
5361917
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| Appearance |
Typically exists as solid at room temperature
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| Melting Point |
237-239ºC
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| LogP |
3.025
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
27
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| Complexity |
664
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C[N+]1(CC[C@@]23C4=C5C=CC(=C4O[C@H]3C(=O)CC[C@]2([C@H]1C5)O)[O-])CC6CC6.Br
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| InChi Key |
IFGIYSGOEZJNBE-KNLJMPJLSA-N
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| InChi Code |
InChI=1S/C21H25NO4.BrH/c1-22(11-12-2-3-12)9-8-20-17-13-4-5-14(23)18(17)26-19(20)15(24)6-7-21(20,25)16(22)10-13;/h4-5,12,16,19,25H,2-3,6-11H2,1H3;1H/t16-,19+,20+,21-,22?;/m1./s1
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| Chemical Name |
(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium-7-one;bromide
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| Synonyms |
MOA-728; MOA728; Methylnaltrexone bromide; Naltrexone methobromide; Relistor; N-Methylnaltrexone Bromide; MRZ-2663BR; bromuro de metilnaltrexona; ...; 73232-52-7; MOA 728
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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 | 2.2918 mL | 11.4590 mL | 22.9179 mL | |
| 5 mM | 0.4584 mL | 2.2918 mL | 4.5836 mL | |
| 10 mM | 0.2292 mL | 1.1459 mL | 2.2918 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04083651 | WITHDRAWN | Drug: Methylnaltrexone bromide Drug: Placebo |
Pancreatic Cancer | Bausch Health Americas, Inc | 2020-01-06 | Phase 2 Phase 3 |
| NCT01004393 | COMPLETEDWITH RESULTS | Drug: Methylnaltrexone bromide | Constipation Neoplasms Opioid-Related Disorders |
University of Vermont | 2009-10 | Phase 2 |
| NCT00672139 | COMPLETEDWITH RESULTS | Drug: Methylnaltrexone bromide | Opioid-Induced Constipation | Bausch Health Americas, Inc | 2008-07 | Phase 4 |
| NCT04787848 | RECRUITING | Drug: Relistor Injectable Product | Chronic Widespread Pain | University of Alabama at Birmingham | 2021-11-15 | Not Applicable |
| NCT04151719 | WITHDRAWN | Drug: Methylnaltrexone bromide (MNTX) | Pancreatic Cancer | Bausch Health Americas, Inc. | 2020-02-03 | Phase 3 |
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