Erythrityl tetranitrate

Identification

Generic Name
Erythrityl tetranitrate
DrugBank Accession Number
DB01613
Background

A vasodilator with general properties similar to nitroglycerin. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1020)

Type
Small Molecule
Groups
Approved, Experimental, Investigational
Structure
Thumb
Weight
Average: 302.11
Monoisotopic: 301.998221676
Chemical Formula
C4H6N4O12
Synonyms
  • (2R*,3S)-rel-1,2,3,4-butanetetroltetranitrate
  • 1,2,3,4-Butanetetralyl tetranitrate
  • Eritrityl tetranitrate
  • Eritrityli tetranitras
  • Erythritol tetranitrate
  • Erythrityl tetranitrate
  • Erythrol tetranitrate
  • ETN
  • Meso-erythritol tetranitrate
  • Tetranitrate d'eritrityle
  • Tetranitrato de eritritilo
  • Tetranitrin
  • Tetranitrol
External IDs
  • NSC-106566

Pharmacology

Indication

For the prevention of angina.

Pharmacology
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Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Erythrityl Tetranitrate is a vasodilator with general properties similar to nitroglycerin.

Mechanism of action

Similar to other nitrites and organic nitrates, erythrityl tetranitrate is converted to an active intermediate compound which activates the enzyme guanylate cyclase. This stimulates the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP) which then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells, eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber. The subsequent release of calcium ions results in the relaxation of the smooth muscle cells and vasodilation.

TargetActionsOrganism
AAtrial natriuretic peptide receptor 1
agonist
Humans
AAtrial natriuretic peptide receptor 2
agonist
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Symptoms of overdose include increased intracranial pressure, with any or all of persistent throbbing headache, confusion, and moderate fever; Vertigo; Palpitations; Visual disturbances; Nausea and vomiting (possibly with colic and even bloody diarrhea); Syncope (especially in the upright posture); Air hunger and dyspnea, later followed by reduced ventilatory effort; Diaphoresis, with the skin either flushed or cold and clammy; Heart block and bradycardia; Paralysis; Coma; Seizures; Death.

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
AmiodaroneAmiodarone may increase the vasodilatory activities of Erythrityl tetranitrate.
AmlodipineAmlodipine may increase the vasodilatory activities of Erythrityl tetranitrate.
AvanafilThe risk or severity of hypotension can be increased when Avanafil is combined with Erythrityl tetranitrate.
BepridilBepridil may increase the vasodilatory activities of Erythrityl tetranitrate.
CarvedilolCarvedilol may increase the vasodilatory activities of Erythrityl tetranitrate.
CinnarizineCinnarizine may increase the vasodilatory activities of Erythrityl tetranitrate.
ClevidipineClevidipine may increase the vasodilatory activities of Erythrityl tetranitrate.
CyclandelateCyclandelate may increase the vasodilatory activities of Erythrityl tetranitrate.
DiltiazemDiltiazem may increase the vasodilatory activities of Erythrityl tetranitrate.
DipyridamoleThe risk or severity of hypotension can be increased when Dipyridamole is combined with Erythrityl tetranitrate.
Interactions
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Food Interactions
  • Avoid alcohol.
  • Take on an empty stomach. Take at least 1 hour before or 2 hours after meals.

Products

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International/Other Brands
Cardilate

Categories

ATC Codes
C01DA63 — Eritrityl tetranitrate, combinationsC01DA13 — Eritrityl tetranitrate
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as alkyl nitrates. These are organic compounds containing a nitrate that is O-linked to an alkyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organic oxoanionic compounds
Sub Class
Organic nitrates
Direct Parent
Alkyl nitrates
Alternative Parents
Organic nitro compounds / Organic nitric acids and derivatives / Organooxygen compounds / Organic oxides / Organic nitrogen compounds / Hydrocarbon derivatives
Substituents
Aliphatic acyclic compound / Alkyl nitrate / Allyl-type 1,3-dipolar organic compound / Hydrocarbon derivative / Organic 1,3-dipolar compound / Organic nitric acid or derivatives / Organic nitro compound / Organic nitrogen compound / Organic oxide / Organooxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
nitrate ester (CHEBI:60072)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
35X333P19D
CAS number
7297-25-8
InChI Key
SNFOERUNNSHUGP-ZXZARUISSA-N
InChI
InChI=1S/C4H6N4O12/c9-5(10)17-1-3(19-7(13)14)4(20-8(15)16)2-18-6(11)12/h3-4H,1-2H2/t3-,4+
IUPAC Name
(2S,3R)-1,3,4-tris(nitrooxy)butan-2-yl nitrate
SMILES
[O-][N+](=O)OC[C@@H](O[N+]([O-])=O)[C@H](CO[N+]([O-])=O)O[N+]([O-])=O

References

General References
Not Available
Human Metabolome Database
HMDB0015551
PubChem Compound
5284553
PubChem Substance
46508990
ChemSpider
4447608
RxNav
4040
ChEBI
60072
ChEMBL
CHEMBL2107583
ZINC
ZINC000018178475
Therapeutic Targets Database
DAP001060
PharmGKB
PA164746528
Wikipedia
Erythrityl_Tetranitrate

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)61 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.195 mg/mLALOGPS
logP1.68ALOGPS
logP1.23ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)-5.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area220.2 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity53.25 m3·mol-1ChemAxon
Polarizability20.27 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.7733
Blood Brain Barrier+0.9089
Caco-2 permeable-0.5825
P-glycoprotein substrateNon-substrate0.7905
P-glycoprotein inhibitor INon-inhibitor0.6464
P-glycoprotein inhibitor IINon-inhibitor0.8955
Renal organic cation transporterNon-inhibitor0.835
CYP450 2C9 substrateNon-substrate0.9002
CYP450 2D6 substrateNon-substrate0.8936
CYP450 3A4 substrateNon-substrate0.5357
CYP450 1A2 substrateNon-inhibitor0.7871
CYP450 2C9 inhibitorNon-inhibitor0.7619
CYP450 2D6 inhibitorNon-inhibitor0.9081
CYP450 2C19 inhibitorNon-inhibitor0.6943
CYP450 3A4 inhibitorNon-inhibitor0.8885
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8212
Ames testAMES toxic0.8896
CarcinogenicityCarcinogens 0.6703
BiodegradationReady biodegradable0.9161
Rat acute toxicity2.7983 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5607
hERG inhibition (predictor II)Non-inhibitor0.9098
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
Yes
Actions
Agonist
General Function
Protein kinase activity
Specific Function
Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis. Has guanylate ...
Gene Name
NPR1
Uniprot ID
P16066
Uniprot Name
Atrial natriuretic peptide receptor 1
Molecular Weight
118918.11 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Schroder H, Noack E: Structure-activity relationship of organic nitrates for activation of guanylate cyclase. Arch Int Pharmacodyn Ther. 1987 Dec;290(2):235-46. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Transmembrane signaling receptor activity
Specific Function
Receptor for the C-type natriuretic peptide NPPC/CNP hormone. Has guanylate cyclase activity upon binding of its ligand. May play a role in the regulation of skeletal growth.
Gene Name
NPR2
Uniprot ID
P20594
Uniprot Name
Atrial natriuretic peptide receptor 2
Molecular Weight
117020.97 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Lange K, Koenig A, Roegler C, Seeling A, Lehmann J: NO donors. Part 18: Bioactive metabolites of GTN and PETN--synthesis and vasorelaxant properties. Bioorg Med Chem Lett. 2009 Jun 1;19(11):3141-4. doi: 10.1016/j.bmcl.2008.04.057. Epub 2008 Apr 26. [Article]

Drug created on August 29, 2007 20:04 / Updated on February 21, 2021 18:51