Virodhamine is an endocannabinoid that modulates neurotransmission by activating cannabinoid (CB) receptors. Virodhamine is a CB1 receptor antagonist and a CB2 receptor agonist. Virodhamine induces megakaryocyte differentiation by triggering MAPK signaling and ROS production. Virodhamine is used to treat various neurological disorders, such as AD/Alzheimer's disease and PD/Parkinson's disease.

Physicochemical Properties

Molecular Formula	C22H37NO2
Molecular Weight	347.53
Exact Mass	347.282
CAS #	287937-12-6
PubChem CID	5712057
Appearance	Yellow to brown viscous liquid
LogP	6.334
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	17
Heavy Atom Count	25
Complexity	408
Defined Atom Stereocenter Count	0
SMILES	CCCCC/C=C/C/C=C/C/C=C/C/C=C/CCCC(OCCN)=O
InChi Key	DLHLOYYQQGSXCC-DOFZRALJSA-N
InChi Code	InChI=1S/C22H37NO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-22(24)25-21-20-23/h6-7,9-10,12-13,15-16H,2-5,8,11,14,17-21,23H2,1H3/b7-6-,10-9-,13-12-,16-15-
Chemical Name	2-aminoethyl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate
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
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Adherence, membrane expansion, and nucleus size are all increased by viteodhamine (50 nM; 72 hours)[1]. Virodhamine (10–40 μM; 72 h) raises TRPV1 and CD61 expression levels[1]. Virodhamine (72 hours) dramatically raises the percentage of high ploidy cells relative to control and inhibits the proliferation of megakaryocyte cells[1]. In megakaryocytic cells, virodhamine dramatically raises the expression of the CB2 receptor protein, ROS generation, and NAPDH oxidase NOX4[1].
ln Vivo	Virodhamine (1-10 mg/kg; ip once) restores the nicotine (0.8 mg/kg) and immobilization stress caused anxiety in vivo[2].
Cell Assay	RT-PCR[1] Cell Types: Megakaryocyte cell line Tested Concentrations: 10, 20 and 40 μM Incubation Duration: 72 h Experimental Results: Dose-dependently enhanced the expression level of megakaryocytic marker CD61 and the expression of TRPV1 mRNA.
Animal Protocol	Animal/Disease Models: Male ICR mice with nicotine (0.8 mg/kg) and immobilization stress induced anxiety[2] Doses: 1, 5 and 10 mg/kg Route of Administration: intraperitoneal (ip) injection; 1-10 mg/kg; once Experimental Results: Dramatically repaired the working memory impairment-like behaviors at a does of 5 mg/kg and demonstrated significant anxiolytic-like effects against the anxiety-like behaviors at a does of 10 mg/kg.
References	[1]. Virodhamine, an endocannabinoid, induces megakaryocyte differentiation by regulating MAPK activity and function of mitochondria. J Cell Physiol. 2021 Feb;236(2):1445-1453. [2]. Hayase T. Working memory- and anxiety-related behavioral effects of repeated nicotine as a stressor: the role of cannabinoid receptors. BMC Neurosci. 2013 Feb 9;14:20.
Additional Infomation	O-Arachidonoyl ethanolamine is a fatty acid ester.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 100 mg/mL (287.74 mM)

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8774 mL	14.3872 mL	28.7745 mL
	5 mM	0.5755 mL	2.8774 mL	5.7549 mL
	10 mM	0.2877 mL	1.4387 mL	2.8774 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.