Molsidomine is an orally bioactive and long acting vasodilator acting as an NO donor and annexin A2 inhibitor. It is metabolized in the liver to the active metabolite linsidomine, which is an unstable compound that releases nitric oxide (NO) upon decay as the actual vasodilating compound. It inhibits PDGF-induced smooth muscle cell migration, suppresses carotid artery neointima formation, and prevents activated platelet adhesion.

Physicochemical Properties

Molecular Formula	C9H14N4O4
Molecular Weight	242.23
Exact Mass	242.101
CAS #	25717-80-0
PubChem CID	5353788
Appearance	White to off-white solid powder
Melting Point	140-141°C
LogP	2.2
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	4
Heavy Atom Count	17
Complexity	270
Defined Atom Stereocenter Count	0
SMILES	CCO/C(=N/C1=C[N+](=NO1)N2CCOCC2)/[O-]
InChi Key	XLFWDASMENKTKL-UHFFFAOYSA-N
InChi Code	InChI=1S/C9H14N4O4/c1-2-16-9(14)10-8-7-13(11-17-8)12-3-5-15-6-4-12/h7H,2-6H2,1H3
Chemical Name	(1E)-1-ethoxy-N-(3-morpholin-4-yloxadiazol-3-ium-5-yl)methanimidate
Synonyms	N-(Ethoxycarbonyl)-3-(4-morpholinyl)sydnone imine Morsydomine SIN10 SIN-10 SIN 10Corvaton
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

ADME/Pharmacokinetics

Absorption, Distribution and Excretion Peak plasma drug concentration (tmax) occurs from 1 to 2 hours after administration. 98 L renal excretion is the main route of elimination of the metabolites in humans (90% to 95%) About 2% of the ingested drug is excreted unchanged in the urine. Metabolism / Metabolites Molsidomine hepatically metabolized to _linsidomine_. Linsidomine releases nitric oxide (NO) from endothelial cells when it decays, and acts as the active vasodilating metabolite responsible for molsidomine's pharmacological effects. Oral absorption of Molsidomine is found to be 95.5% ±4.5. Presystemic metabolism is noted to be 56% and metabolism is reported extensive by Liver. Renal Excretion accounts for 95 % and plasma half-life is 5 hr. Back to top

Additional Infomation

1-ethoxy-N-[3-(4-morpholinyl)-5-oxadiazol-3-iumyl]methanimidate is a member of morpholines. Molsidomine is an orally active, long-acting vasodilator, which belongs to the class of medications known as syndnones. Interestingly, it is being studied as being a preventive measure in cerebral infarction. A morpholinyl sydnone imine ethyl ester, having a nitrogen in place of the keto oxygen. It acts as NITRIC OXIDE DONORS and is a vasodilator that has been used in ANGINA PECTORIS. Drug Indication The indications for use of molsidomine include ischemic heart disease, angina, chronic heart failure, and pulmonary hypertension. Mechanism of Action Molsidomine, a cardiovascular drug, acts in a similar fashion to organic nitrates. The SIN-1A metabolite of molsidomine has a pharmacologically active group of nitric oxide, which increases levels of cyclic GMP, and decreases intracellular calcium ions in smooth muscle cells. This leads to relaxation of smooth muscle in the blood vessels, and inhibits platelet aggregation.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 100 mg/mL (~412.83 mM) H2O : ~25 mg/mL (~103.21 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (10.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 25 mg/mL (103.21 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.1283 mL	20.6415 mL	41.2831 mL
	5 mM	0.8257 mL	4.1283 mL	8.2566 mL
	10 mM	0.4128 mL	2.0642 mL	4.1283 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.