| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Purity: ≥98%
Naldemedine (formerly known as S-297,995; S297995; trade name: Symproic) is a potent, orally bioavailable peripherally active, and selective μ-opioid receptor antagonist developed by Shionogi and has been approved in 2017 for the treatment of opioid-induced constipation in adult patients with chronic non-cancer pain. Clinical studies have thus far found it to possess statistically significant effectiveness for these indications and to be generally well-tolerated with predominantly mild to moderate gastrointestinal side effects. No effects indicative of central opioid withdrawal or impact on the analgesic or miotic effects of co-administered opioids have been observed.
| ln Vivo |
In rats, nalidezemedine (oral gavage; 0.03–10 mg/kg; once) prevents the opioid-induced suppression of morphine and oxycodone subcutaneous transit on the small intestine [2].
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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:Inhibition of subcutaneousmorphine-induced inhibition of intestinal transport in rats , ED50 is 0.03 mg/kg, inhibits oxycodone-induced inhibition model, ED50 is 0.02 mg/kg. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Tmax is 0.75 h. Administration with a high-fat meal reduces Cmax by 35% and increases Tmax to 2.5 h. 57% of naldemedine is excreted in the urine with 16-18% as the parent compound and 35% is excreted in the feces. The apparent volume of disribution during the terminal phase is 155 L Metabolism / Metabolites Naldemedine is mainly metabolized to nor-naldemedine by CYP3A. Some metabolism to naldemedine-3-glucuronide occurs via UGT1A3. Both metabolites are acitive but less potent than naldemedine. The relative exposures of these metabolites are 9-13% and <3% for nor-naldemedine and naldemedine-3-glucuronide respectively. Naldemedine is also cleaved in the intestine to form benzamidine and naldemedine carboxylic acid. Biological Half-Life The terminal elimination half life is 11 h. |
| Toxicity/Toxicokinetics |
Hepatotoxicity
Therapy with naldemedine has not been linked to serum enzyme elevations or to clinically apparent liver injury. In preregistration studies, liver test abnormalities arose in less than 1% of treated patients but were transient, mild and not associated with symptoms. There were no reported cases of liver injury with jaundice or symptoms. Since its approval and more widescale use, there have been no published reports of hepatotoxicity attributed to naldemedine. Likelihood score: E (unlikely cause of clinically apparent liver injury). Protein Binding Naldemedine is 93-94% bound to human plasma proteins. |
| References |
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| Additional Infomation |
Naldemedine is an opioid receptor antagonist. It is a modified form of [DB00704] to which a side chain has been added to increase molecular weight and polar surface area resulting in restricted transport across the blood brain barrier. Naldemedine was approved in 2017 in both the US and Japan for the treatment of Opioid-induced Constipation.
Naldemedine is an Opioid Antagonist. The mechanism of action of naldemedine is as an Opioid Antagonist. Naldemedine is a peripherally acting opioid antagonist which is used to treat constipation caused by chronic opioid use. Naldemedine has not been linked to serum enzyme elevations during therapy or to clinically apparent liver injury. See also: Naldemedine Tosylate (active moiety of). Drug Indication For the treatment of opioid-induced constipation. FDA Label Rizmoic is indicated for the treatment of opioid-induced constipation (OIC) in adult patients who have previously been treated with a laxative. Treatment of opioid-induced constipation (OIC) Mechanism of Action Naldemedine binds to and antagonizes mu-, delta-, and kappa-opioid receptors. The binding of opioid agonists to peripheral mu-opioid receptors slows the transit of feces through the intestine resulting in constipation. By antagonizing mu-opioid receptors, naldemedine inhibits this effect. Pharmacodynamics Naldemedine is an opioid receptor antagonist with restricted movement across the blood brain barrier. This allows it to antagonize the periperal effects of opioid drugs such as constipation without interfering with the effects on the central nervous system. |
| Molecular Formula |
C32H34N4O6
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|---|---|
| Molecular Weight |
570.635568141937
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| Exact Mass |
570.247
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| CAS # |
916072-89-4
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| Related CAS # |
Naldemedine tosylate;1345728-04-2
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| PubChem CID |
54732242
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
42
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| Complexity |
1140
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| Defined Atom Stereocenter Count |
4
|
| SMILES |
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 |
AXQACEQYCPKDMV-RZAWKFBISA-N
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| InChi Code |
InChI=1S/C32H34N4O6/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/h3-7,10-11,17,22,26,37-38,40H,8-9,12-16H2,1-2H3,(H,34,39)/t22-,26+,31+,32-/m1/s1
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| Chemical Name |
17-(cyclopropylmethyl)-6,7-didehydro-4,5alpha-epoxy-3,6,14-trihydroxy-N-(2-(3-phenyl- 1,2,4-oxadiazol-5-yl)propan-2-yl)morphinan-7-carboxamide
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| Synonyms |
S-297,995; S297,995; S 297995; S-297995; S297995; S 297,995; trade name: Symproic
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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) |
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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 | 1.7524 mL | 8.7621 mL | 17.5242 mL | |
| 5 mM | 0.3505 mL | 1.7524 mL | 3.5048 mL | |
| 10 mM | 0.1752 mL | 0.8762 mL | 1.7524 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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