| 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
The time to peak concentration (Tmax) is 0.75 hours. Concomitant administration with a high-fat meal reduces Cmax by 35% and prolongs Tmax to 2.5 hours. 57% of nalmediline is excreted in the urine, of which 16-18% is the unchanged drug and 35% is excreted in the feces. The apparent volume of distribution in the terminal phase is 155 L/h. Metabolism/Metabolites Namediline is primarily metabolized to nornalmediline via CYP3A. Some metabolites are metabolized to nalmediline-3-glucuronide via UGT1A3. Both metabolites are active, but less potent than nalmediline. The relative exposures of these metabolites are: nornalmediline 9-13%, nalmediline-3-glucuronide <3%. Namediline also breaks down in the intestine to produce benzoamidine and namediline carboxylic acid. Biological half-life The terminal elimination half-life is 11 hours. |
| Toxicity/Toxicokinetics |
Hepatotoxicity
Nalmediline treatment was not associated with elevated serum enzymes or clinically significant liver injury. In pre-registration studies, less than 1% of treated patients experienced abnormal liver function, but these abnormalities were transient, mild, and asymptomatic. No cases of liver injury with jaundice or other symptoms have been reported. Since nalmediline was approved and widely used, there have been no published reports of it causing hepatotoxicity. Probability Score: E (Unlikely to be a cause of clinically significant liver injury). Protein Binding Nalmediline binds to human plasma proteins in 93-94% of cases. |
| References |
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| Additional Infomation |
Nalmediline is an opioid receptor antagonist. It is a modified form of [DB00704], which increases molecular weight and polar surface area by adding a side chain, thereby restricting its crossing of the blood-brain barrier. Nalmediline was approved in the United States and Japan in 2017 for the treatment of opioid-induced constipation. Nalmediline is an opioid receptor antagonist. The mechanism of action of nalmediline is as an opioid receptor antagonist. Nalmediline is a peripherally acting opioid receptor antagonist used to treat constipation caused by chronic opioid use. No increase in serum enzymes or clinically significant liver injury has been observed with nalmediline during treatment. See also: Nalmediline tosylate (active ingredient).
Drug Indications For the treatment of opioid-induced constipation. FDA Label Rimoidin is indicated for the treatment of opioid-induced constipation (OIC) in adult patients with a history of laxative therapy. Treatment of Opioid-Induced Constipation (OIC) Mechanism of Action Nalmediline binds to and antagonizes the effects of μ, δ, and κ opioid receptors. Opioid agonists bind to peripheral μ-opioid receptors, slowing the passage of feces through the intestines, thus leading to constipation. Nalmediline inhibits this effect by antagonizing μ-opioid receptors. Pharmacodynamics Nalmediline is an opioid receptor antagonist whose transport across the blood-brain barrier is restricted. This allows it to antagonize the peripheral effects of opioids, such as constipation, without interfering with central nervous system activity. |
| Molecular Formula |
C32H34N4O6
|
|---|---|
| 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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