| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Targets are μ-, δ-, and κ-opioid receptors, with high binding affinity (Ki = 0.34 nM for μ-opioid receptor); naldemedine acts as a peripherally acting μ-opioid receptor antagonist in tissues, blocking opioid-induced inhibition of gastrointestinal motility without reversing central analgesia.
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|---|---|
| ln Vitro |
Naldemedine binds μ-, δ-, and κ-opioid receptors with high affinity (μ-opioid receptor Ki = 0.34 nM) and antagonizes μ-opioid receptor-mediated signaling in peripheral tissues; in vitro, it reverses opioid-induced inhibition of gastrointestinal motility and secretion in isolated tissue preparations.
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| ln Vivo |
Naldemidine tosylate (oral gavage; 0.03-10 mg/kg; once) reduces opioid-induced reduction of intestinal transit in rats [2].
In vivo, naldemedine tosylate reverses opioid-induced constipation in animal models and humans without crossing the blood–brain barrier to reverse analgesia; it increases gastrointestinal transit and stool frequency in opioid-treated rodents, and it is clinically used for OIC in adults with chronic non-cancer pain. |
| Enzyme Assay |
Opioid receptor binding is measured using membrane preparations expressing μ-, δ-, or κ-opioid receptors and a suitable radioligand (e.g., [3H]DAMGO for μ); graded naldemedine concentrations displace the radioligand, and Ki values are calculated; selectivity is assessed across the three opioid receptor subtypes, and peripheral restriction is confirmed by measuring brain penetration in vivo.
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| Cell Assay |
Isolated guinea pig ileum or mouse colon preparations are treated with opioids in the presence or absence of naldemedine, and electrically stimulated contractions are measured to assess reversal of opioid-induced inhibition; cell-based assays use opioid receptor-expressing cells to measure cAMP inhibition or GTPγS binding.
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| Animal Protocol |
Animal/Disease Models: 6weeks old Wistar and SD male rats [2]
Doses: 0.03-10 mg/kg Route of Administration: po (oral gavage); 0.03-10 mg/kg; Experimental Results:subcutaneousinhibition of small intestinal transport in rats, ED50 is 0.03 mg/kg Mice or rats receive opioids to induce constipation and are treated with naldemedine tosylate by oral gavage at doses selected from pharmacokinetic studies; gastrointestinal transit is measured by charcoal meal or fluorescent bead transit, stool frequency and weight are recorded, and brain and plasma drug concentrations are measured to confirm peripheral restriction and lack of central opioid antagonism. |
| References |
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| Additional Infomation |
See also: Naldemedine (with active fraction).
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| Molecular Formula |
C39H42N4O9S
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|---|---|
| Molecular Weight |
742.83718919754
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| Exact Mass |
742.267
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| CAS # |
1345728-04-2
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| Related CAS # |
Naldemedine;916072-89-4
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| PubChem CID |
56837137
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.58
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
53
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| Complexity |
1340
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CC1=CC=C(C=C1)S(=O)(=O)O.CC(C)(C1=NC(=NO1)C2=CC=CC=C2)NC(=O)C3=C([C@H]4[C@@]56CCN([C@@H]([C@@]5(C3)O)CC7=C6C(=C(C=C7)O)O4)CC8CC8)O
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| InChi Key |
WCYDLROFMZJJLE-RTMHEQJQSA-N
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| InChi Code |
InChI=1S/C32H34N4O6.C7H8O3S/c1-30(2,29-33-27(35-42-29)18-6-4-3-5-7-18)34-28(39)20-15-32(40)22-14-19-10-11-21(37)25-23(19)31(32,26(41-25)24(20)38)12-13-36(22)16-17-8-9-17;1-6-2-4-7(5-3-6)11(8,9)10/h3-7,10-11,17,22,26,37-38,40H,8-9,12-16H2,1-2H3,(H,34,39);2-5H,1H3,(H,8,9,10)/t22-,26+,31+,32-;/m1./s1
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| Chemical Name |
(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,7,9-trihydroxy-N-[2-(3-phenyl-1,2,4-oxadiazol-5-yl)propan-2-yl]-1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-6-carboxamide;4-methylbenzenesulfonic acid
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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 (e.g. under nitrogen), 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: ~50 mg/mL (~67.3 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.37 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: ≥ 2.5 mg/mL (3.37 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (3.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3462 mL | 6.7309 mL | 13.4618 mL | |
| 5 mM | 0.2692 mL | 1.3462 mL | 2.6924 mL | |
| 10 mM | 0.1346 mL | 0.6731 mL | 1.3462 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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