Molsidomine

Identification

Summary

Molsidomine is a long-acting vasodilator used to treat angina pectoris, including in association with left heart failure and acute myocardial infarction.

Generic Name
Molsidomine
DrugBank Accession Number
DB09282
Background

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 1.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 242.235
Monoisotopic: 242.101504947
Chemical Formula
C9H14N4O4
Synonyms
  • Molsidomina
  • Molsidomine
  • Molsidominum
External IDs
  • CAS 276
  • CAS-276
  • SIN-10

Pharmacology

Indication

The indications for use of molsidomine include ischemic heart disease, angina, chronic heart failure, and pulmonary hypertension 9,10.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Molsidomine leads to smooth muscle relaxation in the coronary blood vessels, relieving symptoms of angina and increasing blood flow to the coronary arteries.

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.

TargetActionsOrganism
UGuanylate cyclase soluble subunit alpha-2
agonist
Humans
Absorption

Peak plasma drug concentration (tmax) occurs from 1 to 2 hours after administration.

Volume of distribution

98 L 8

Protein binding

Not Available

Metabolism

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

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Route of elimination

Not Available

Half-life

Not Available

Clearance

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.

Adverse Effects
Adverseeffects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcebutololMolsidomine may increase the hypotensive activities of Acebutolol.
AliskirenMolsidomine may increase the hypotensive activities of Aliskiren.
AmbrisentanMolsidomine may increase the hypotensive activities of Ambrisentan.
AmlodipineMolsidomine may increase the hypotensive activities of Amlodipine.
Amyl NitriteMolsidomine may increase the hypotensive activities of Amyl Nitrite.
AtenololMolsidomine may increase the hypotensive activities of Atenolol.
AvanafilMolsidomine may increase the hypotensive activities of Avanafil.
Azilsartan medoxomilMolsidomine may increase the hypotensive activities of Azilsartan medoxomil.
BenazeprilMolsidomine may increase the hypotensive activities of Benazepril.
BendroflumethiazideMolsidomine may increase the hypotensive activities of Bendroflumethiazide.
Interactions
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Food Interactions
Not Available

Products

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International/Other Brands
Angoral (Pharmaghreb) / Cardamine (ADWYA) / Corvasal (Benta) / Dilacor (Saiph) / Molsicor (IBN) / Molsidomina Polfa (Polfa) / Molsidomine Arrow (Arrow)

Categories

ATC Codes
C01DX12 — Molsidomine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as morpholines. These are organic compounds containing a morpholine moiety, which consists of a six-member aliphatic saturated ring with the formula C4H9NO, where the oxygen and nitrogen atoms lie at positions 1 and 4, respectively.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Oxazinanes
Sub Class
Morpholines
Direct Parent
Morpholines
Alternative Parents
Organic carbonic acids and derivatives / Propargyl-type 1,3-dipolar organic compounds / Oxacyclic compounds / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Aliphatic heteromonocyclic compound / Azacycle / Carbonic acid derivative / Carbonyl group / Dialkyl ether / Ether / Hydrocarbon derivative / Morpholine / Organic 1,3-dipolar compound / Organic nitrogen compound
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
D46583G77X
CAS number
25717-80-0
InChI Key
XLFWDASMENKTKL-UHFFFAOYSA-N
InChI
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
IUPAC Name
5-[(ethoxycarbonyl)azanidyl]-3-(morpholin-4-yl)-1,2,3lambda5-oxadiazol-3-ylium
SMILES
CCOC(=O)[N-]C1=C[N+](=NO1)N1CCOCC1

References

General References
  1. Ehlert A, Schmidt C, Wolfer J, Manthei G, Jacobs AH, Bruning R, Heindel W, Ringelstein EB, Stummer W, Pluta RM, Hesselmann V: Molsidomine for the prevention of vasospasm-related delayed ischemic neurological deficits and delayed brain infarction and the improvement of clinical outcome after subarachnoid hemorrhage: a single-center clinical observational study. J Neurosurg. 2016 Jan;124(1):51-8. doi: 10.3171/2014.12.JNS13846. Epub 2015 Jul 10. [Article]
  2. Lorenc-Koci E, Czarnecka A, Lenda T, Kaminska K, Konieczny J: Molsidomine, a nitric oxide donor, modulates rotational behavior and monoamine metabolism in 6-OHDA lesioned rats treated chronically with L-DOPA. Neurochem Int. 2013 Dec;63(8):790-804. doi: 10.1016/j.neuint.2013.09.021. Epub 2013 Sep 30. [Article]
  3. Rosenkranz B, Winkelmann BR, Parnham MJ: Clinical pharmacokinetics of molsidomine. Clin Pharmacokinet. 1996 May;30(5):372-84. [Article]
  4. Ostrowski J, Resag K: Pharmacokinetics of molsidomine in humans. Am Heart J. 1985 Mar;109(3 Pt 2):641-3. [Article]
  5. Molsidomine [Link]
  6. Update: Molsidomine [Link]
  7. EPA Chemistry Dashboard: Molsidomine [Link]
  8. Molsidomine [Link]
  9. Molsidomide: an overview [Link]
  10. Molsidomine [Link]
  11. Relationship between pharmacokinetics and pharmacodynamics of molsidomine and its metabolites in humans [Link]
  12. Molsidomine 2/4 mg tablets [Link]
  13. Clinical Pharmacology of Antianginal Drugs [Link]
KEGG Drug
D01320
PubChem Compound
5353788
PubChem Substance
310265175
ChemSpider
4090
BindingDB
39912
RxNav
7023
ChEBI
92623
ChEMBL
CHEMBL1329455
Wikipedia
Molsidomine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAtherosclerosis / Chronic Stable Angina Pectoris1
Not AvailableCompletedTreatmentMyocardial Ischemia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet2 MG
Tablet4 MG
Tablet, extended releaseOral8 MG
Tablet
Tablet, extended releaseOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)156[L1368]
boiling point (°C)266 to 368[L1368]
water solubility4.65e-03 to 1.74[L1368]
logP-1.61 [L1368]
Predicted Properties
PropertyValueSource
Water Solubility13.3 mg/mLALOGPS
logP-1ALOGPS
logP-1ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)9.94ChemAxon
pKa (Strongest Basic)-3.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area77.91 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity76.99 m3·mol-1ChemAxon
Polarizability23.94 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Heme binding
Specific Function
Has guanylyl cyclase on binding to the beta-1 subunit.Isoform 2 acts as a negative regulator of guanylyl cyclase activity as it forms non-functional heterodimers with the beta subunits.
Gene Name
GUCY1A2
Uniprot ID
P33402
Uniprot Name
Guanylate cyclase soluble subunit alpha-2
Molecular Weight
81749.185 Da
References
  1. Kukovetz WR, Holzmann S: Mechanism of vasodilation by molsidomine. Am Heart J. 1985 Mar;109(3 Pt 2):637-40. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Heme binding
Specific Function
Has guanylyl cyclase on binding to the beta-1 subunit.Isoform 2 acts as a negative regulator of guanylyl cyclase activity as it forms non-functional heterodimers with the beta subunits.
Gene Name
GUCY1A2
Uniprot ID
P33402
Uniprot Name
Guanylate cyclase soluble subunit alpha-2
Molecular Weight
81749.185 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Metal ion binding
Specific Function
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, ...
Gene Name
PDE5A
Uniprot ID
O76074
Uniprot Name
cGMP-specific 3',5'-cyclic phosphodiesterase
Molecular Weight
99984.14 Da

Drug created on October 29, 2015 16:02 / Updated on May 07, 2021 21:07