| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
R-1 Methanandamide Phosphate is a prodrug that targets cannabinoid receptors CB1 and CB2 after enzymatic conversion to the active parent compound, R-1 methanandamide. The prodrug itself may have minimal activity at these receptors. Upon cleavage of the phosphate group by endogenous phosphatases (e.g., alkaline phosphatase, tissue-nonspecific alkaline phosphatase), the active parent R-1 methanandamide is released. R-1 methanandamide is a stable analog of anandamide (with a methyl group that blocks fatty acid amide hydrolase-mediated degradation) and acts as a potent and selective agonist of the CB1 cannabinoid receptor (Ki ~20 nM for CB1; also activates CB2). The parent compound is essentially equivalent in activity to anandamide itself.
|
|---|---|
| ln Vitro |
In vitro, R-1 Methanandamide Phosphate is used as a water-soluble prodrug analog of the endocannabinoid arachidonoylethanolamide (AEA). The activity of R-1MAP in cell-based assays is essentially equivalent to that of AEA or R-1 methanandamide after phosphatase-mediated conversion. For example, R-1MAP exhibited essentially equivalent activity to AEA in inhibiting the growth of C6 glioma cells. This suggests that the phosphate prodrug is efficiently converted to the active parent compound in cells, allowing researchers to deliver a water-soluble, stable formulation of anandamide to cells and tissues without the solubility or stability limitations of the parent cannabinoid.
|
| ln Vivo |
In vivo, R-1 Methanandamide Phosphate serves as a water-soluble prodrug analog of anandamide, enabling convenient aqueous formulation for injection. The phosphate ester is designed to be cleaved in vivo by endogenous phosphatases, releasing the active parent R-1 methanandamide. This prodrug approach overcomes the poor water solubility and metabolic instability of the parent cannabinoid, allowing better bioavailability and more reproducible dosing in animal studies. The released parent compound activates CB1 receptors in the brain and peripheral tissues, producing cannabinoid-like effects (analgesia, hypothermia, catalepsy, reduced locomotor activity). Specific pharmacokinetic and pharmacodynamic data are limited.
|
| Enzyme Assay |
Cell-free assays for this compound are not typically performed, as the phosphate prodrug requires enzymatic cleavage by phosphatases to release the active parent cannabinoid. If desired, alkaline phosphatase from bovine intestinal mucosa can be used to pre-treat the prodrug in vitro to generate R-1 methanandamide, which can then be tested in standard cannabinoid receptor binding assays using membrane preparations from cells expressing recombinant CB1 or CB2 receptors. [3H]-CP-55,940 or [3H]-WIN-55,212-2 are commonly used radioligands.
|
| Cell Assay |
Cell-based cannabinoid activity assay: Cells expressing cannabinoid receptors (e.g., CB1-expressing CHO cells or primary neurons) are seeded in 96-well plates. R-1 Methanandamide Phosphate is added at various concentrations (e.g., 0.01-10 microM) and incubated for 30-60 minutes to allow cellular phosphatase-mediated conversion to the active parent compound. Functional readouts include inhibition of forskolin-stimulated cAMP accumulation (CB1-mediated), calcium mobilization, or activation of MAP kinase pathways. The activity should be blocked by the CB1 antagonist rimonabant (SR141716A) to confirm receptor specificity. The prodrug shows essentially equivalent activity to AEA in such assays.
|
| Animal Protocol |
In vivo administration protocol for endocannabinoid prodrugs: R-1 Methanandamide Phosphate can be administered to mice or rats via intravenous (i.v.), intraperitoneal (i.p.), or subcutaneous (s.c.) injection, dissolved in saline or aqueous buffer (the phosphate group confers water solubility). Typical doses range from 0.1-20 mg/kg depending on the desired effect. Cannabinoid-mediated behavioral effects (analgesia measured by tail-flick or hot-plate tests, hypothermia measured by rectal temperature, catalepsy measured by the bar test, and locomotor activity measured in an open field) are assessed at various time points post-injection. Effects should be blocked by a CB1 antagonist.
|
| ADME/Pharmacokinetics |
As a water-soluble prodrug, R-1 Methanandamide Phosphate is expected to have good bioavailability following intraperitoneal, subcutaneous, or intravenous administration due to its aqueous solubility. The phosphate group is cleaved by endogenous phosphatases in plasma and tissues to release the active parent compound R-1 methanandamide. The parent compound is metabolically stabilized against fatty acid amide hydrolase (FAAH)-mediated degradation due to the methyl group at the 1' position, resulting in a longer duration of action compared to anandamide. Detailed PK parameters (t1/2, Cmax, AUC) have not been reported for this specific prodrug.
|
| Toxicity/Toxicokinetics |
Toxicity studies specifically for R-1 Methanandamide Phosphate are not available. The parent compound anandamide and its stable analogs generally have a wide safety margin in animal models, with acute toxicity occurring only at high doses. R-1 methanandamide has been studied extensively and is well-tolerated at doses producing cannabinoid-like behavioral effects. The phosphate ester likely has low inherent toxicity. The prodrug is a research chemical and not intended for human use; standard laboratory safety precautions (avoiding ingestion, inhalation, and skin contact) should be followed.
|
| References |
[1]. Juntunen J, et al. Anandamide prodrugs. 1. Water-soluble phosphate esters of arachidonylethanolamide and R-methanandamide. Eur J Pharm Sci. 2003 May;19(1):37-43.
|
| Additional Infomation |
R-1 formamide phosphate is a type of ethanolamine phosphate.
R-1 Methanandamide Phosphate is not a drug and has no clinical applications or regulatory approval. It is a water-soluble prodrug analog of the endocannabinoid anandamide (AEA), developed for research purposes to overcome the poor water solubility of anandamide and its metabolically stable analogs. By providing water solubility and phosphate-based delivery, this prodrug enables in vivo and in vitro studies of CB1/CB2 cannabinoid receptor activation with improved formulation properties. R-1 Methanandamide (the parent compound after phosphate cleavage) is essentially equivalent in activity to anandamide in cellular assays including inhibition of C6 glioma cell growth. Not for human use. |
| Molecular Formula |
C23H40NO5P
|
|---|---|
| Molecular Weight |
441.54
|
| Exact Mass |
441.264
|
| CAS # |
649569-33-5
|
| PubChem CID |
35026345
|
| Appearance |
Yellow to brown viscous liquid
|
| Density |
1.1±0.1 g/cm3
|
| Index of Refraction |
1.511
|
| LogP |
5.09
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
18
|
| Heavy Atom Count |
30
|
| Complexity |
592
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCC(N[C@@H](COP(O)(O)=O)C)=O
|
| InChi Key |
LONSAFDJFAGAFZ-FQPARAGTSA-N
|
| InChi Code |
InChI=1S/C23H40NO5P/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-23(25)24-22(2)21-29-30(26,27)28/h7-8,10-11,13-14,16-17,22H,3-6,9,12,15,18-21H2,1-2H3,(H,24,25)(H2,26,27,28)/b8-7-,11-10-,14-13-,17-16-/t22-/m1/s1
|
| Chemical Name |
[(2R)-2-[[(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoyl]amino]propyl] dihydrogen phosphate
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 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
|
|---|---|
| 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 | 2.2648 mL | 11.3240 mL | 22.6480 mL | |
| 5 mM | 0.4530 mL | 2.2648 mL | 4.5296 mL | |
| 10 mM | 0.2265 mL | 1.1324 mL | 2.2648 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
