| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
| Targets |
micro-Opioid Receptor (MOR). Loperamide D6 HCl acts as a selective and potent peripheral micro-opioid receptor agonist. By binding to micro-opioid receptors located on the circular and longitudinal intestinal muscle, it reduces peristalsis, increases intestinal transit time, and enhances water and electrolyte absorption in the bowel, resulting in reduced fecal volume and fluid loss.
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| ln Vitro |
Loperamide binds to micro, delta, and kappa opioid receptors with Ki values of 3 nM, 48 nM, and 1156 nM, respectively, showing high selectivity for the micro-receptor. It inhibits electrically evoked contractions of isolated guinea pig ileum (IC50 = 6-10 nM) and reduces prostaglandin E2-induced intestinal fluid secretion in vitro.
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| ln Vivo |
In rodent models of castor oil-induced diarrhea, oral loperamide (0.1-3 mg/kg) significantly reduces the frequency and volume of diarrheal stools in a dose-dependent manner, with an ED50 of approximately 0.5 mg/kg. It also delays gastrointestinal transit of a charcoal meal in mice (ED50 ~0.2 mg/kg). These anti-diarrheal effects occur without significant CNS opioid activity (analgesia, respiratory depression) at therapeutic doses.
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| Enzyme Assay |
Radioligand binding assays are performed using membrane preparations from CHO cells expressing human micro-opioid receptors (MOR). Membranes (20-40 microg protein) are incubated with [3H]DAMGO as the radioligand (0.5-1 nM) and varying concentrations of Loperamide D6 HCl in 50 mM Tris-HCl buffer (pH 7.4) containing 5 mM MgCl2 and 0.5% BSA for 60 min at 25degC. Nonspecific binding is determined with 10 microM naloxone. Bound and free radioligands are separated by filtration through GF/B glass fiber filters, and bound radioactivity is measured by liquid scintillation. Ki values are calculated.
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| Cell Assay |
Guinea pig ileum (GPI) longitudinal muscle myenteric plexus strips are mounted in organ baths containing Krebs buffer at 37degC, gassed with 95% O2/5% CO2. A resting tension of 0.5-1 g is applied. Tissues are stimulated electrically (0.1 Hz, 0.5 ms, supranormal voltage) to elicit twitch contractions. After stable twitches are obtained, cumulative concentration-response curves for Loperamide D6 HCl (0.1-1000 nM) are generated, and IC50 for inhibition of twitch height is calculated. The selective micro-antagonist naloxone (100 nM) is added to confirm receptor specificity.
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| Animal Protocol |
Male Sprague-Dawley rats (200-250 g, fasted overnight) are used. A charcoal meal (5% charcoal in 10% gum arabic, 0.5 mL/rat) is administered orally. Loperamide D6 HCl (0.1-3 mg/kg) or vehicle is given orally 30 min before the charcoal meal. Thirty minutes after the charcoal meal, the rats are sacrificed, and the small intestine is removed. The distance traveled by the charcoal is measured, and the percentage of intestinal transit is calculated as (charcoal distance / total small intestine length) × 100%. The ED50 for inhibition of transit is determined.
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| ADME/Pharmacokinetics |
Loperamide D6 HCl is used as an internal standard (IS) for LC-MS/MS quantification. Loperamide is poorly absorbed orally (bioavailability ~0.3%), with a plasma half-life of 9-14 h in humans. It is 95-97% protein bound, primarily to albumin, and undergoes extensive first-pass metabolism (CYP3A4, CYP2C8). It is excreted in feces (primarily as unchanged drug) and urine (as metabolites).
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| Toxicity/Toxicokinetics |
Loperamide is considered safe enough to be sold over the counter (OTC). Common adverse effects include constipation, abdominal cramps, nausea, dizziness, and dry mouth at high doses. Serious but rare effects (with overdose or abuse): CNS depression (respiratory depression, sedation, coma) and cardiac arrhythmias (QT prolongation, Torsade de Pointes due to hERG blockade). Loperamide D6 HCl is not for human therapeutic use.
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| References | |
| Additional Infomation |
Loperamide (Imodium) was FDA-approved in 1976 for acute and chronic diarrhea, including traveler‘s diarrhea, IBD, and IBS-D. The D6-labeled version is a research standard for LC-MS/MS bioanalysis, drug-drug interaction studies, and investigation of loperamide's ADME profile, particularly concerning its peripheral selectivity, P-glycoprotein (P-gp) efflux (which limits CNS penetration), and the role of CYP3A4 polymorphism in its pharmacokinetics.
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| Molecular Formula |
C29H28D6N2O2CL2
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|---|---|
| Molecular Weight |
519.535430668
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| Exact Mass |
518.237
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| CAS # |
1189469-46-2
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| Related CAS # |
Loperamide hydrochloride;34552-83-5
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| PubChem CID |
45039663
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
623
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C([2H])([2H])([2H])N(C([2H])([2H])[2H])C(=O)C(CCN1CCC(CC1)(C2=CC=C(C=C2)Cl)O)(C3=CC=CC=C3)C4=CC=CC=C4.Cl
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| InChi Key |
PGYPOBZJRVSMDS-TXHXQZCNSA-N
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| InChi Code |
InChI=1S/C29H33ClN2O2.ClH/c1-31(2)27(33)29(24-9-5-3-6-10-24,25-11-7-4-8-12-25)19-22-32-20-17-28(34,18-21-32)23-13-15-26(30)16-14-23;/h3-16,34H,17-22H2,1-2H3;1H/i1D3,2D3;
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| Chemical Name |
4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-2,2-diphenyl-N,N-bis(trideuteriomethyl)butanamide;hydrochloride
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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) |
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 | 1.9248 mL | 9.6239 mL | 19.2478 mL | |
| 5 mM | 0.3850 mL | 1.9248 mL | 3.8496 mL | |
| 10 mM | 0.1925 mL | 0.9624 mL | 1.9248 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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