Identification

Name
Nitric Oxide
Accession Number
DB00435
Description

Nitric oxide or Nitrogen monoxide is a chemical compound with chemical formula NO. This gas is an important signaling molecule in the body of mammals including humans and is an extremely important intermediate in the chemical industry. It is also a toxic air pollutant produced by automobile engines and power plants.

Nitric oxide (NO) should not be confused with nitrous oxide (N2O), a general anaesthetic, or with nitrogen dioxide (NO2) which is another poisonous air pollutant.

The nitric oxide molecule is a free radical, which is relevant to understanding its high reactivity. It reacts with the ozone in air to form nitrogen dioxide, signalled by the appearance of the reddish-brown color.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 30.0061
Monoisotopic: 29.997988627
Chemical Formula
NO
Synonyms
  • EDRF
  • endothelium-derived relaxing factor
  • Mononitrogen monoxide
  • Monóxido de nitrógeno
  • Monoxyde d'azote
  • Nitric oxide
  • Nitrogen monooxide
  • Nitrogen monoxide
  • Nitrosyl
  • óxido de nitrógeno(II)
  • óxido nítrico
  • Oxyde azotique
  • Oxyde nitrique
  • Stickstoff(II)-oxid
  • Stickstoffmonoxid
External IDs
  • OHM-11771

Pharmacology

Indication

For the treatment of term and near-term (>34 weeks) neonates with hypoxic respiratory failure

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Persistent pulmonary hypertension of the newborn (PPHN) occurs as a primary developmental defect or as a condition secondary to other diseases such as meconium aspiration syndrome (MAS), pneumonia, sepsis, hyaline membrane disease, congenital diaphragmatic hernia (CDH), and pulmonary hypoplasia. In these states, pulmonary vascular resistance (PVR) is high, which results in hypoxemia secondary to right-to-left shunting of blood through the patent ductus arteriosus and foramen ovale. In neonates with PPHN, Nitric oxide improves oxygenation (as indicated by significant increases in PaO2). Nitric oxide appears to increase the partial pressure of arterial oxygen (PaO2) by dilating pulmonary vessels in better entilated areas of the lung, redistributing pulmonary blood flow away from lung regions with low ventilation/perfusion (V/Q) ratios toward regions with normal ratios.

Mechanism of action

Nitric oxide is a compound produced by many cells of the body. It relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating guanylate cyclase and increasing intracellular levels of cyclic guanosine 3',5'-monophosphate, which then leads to vasodilation. When inhaled, nitric oxide produces pulmonary vasodilation.

TargetActionsOrganism
AGuanylate cyclase soluble subunit alpha-2
inducer
Humans
UMetallothionein-1ANot AvailableHumans
UIndoleamine 2,3-dioxygenase 1Not AvailableHumans
Absorption

Nitric oxide is absorbed systemically after inhalation.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

via pulmonary capillary bed

Route of elimination

Nitrate has been identified as the predominant nitric oxide metabolite excreted in the urine, accounting for >70% of the nitric oxide dose inhaled.

Half-life

2–6 seconds

Clearance
Not Available
Adverse Effects
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)Disease
Creatine Deficiency, Guanidinoacetate Methyltransferase DeficiencyDisease
Hyperornithinemia with Gyrate Atrophy (HOGA)Disease
Arginine and Proline MetabolismMetabolic
Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)Disease
Hyperprolinemia Type IIDisease
Hyperprolinemia Type IDisease
L-Arginine:Glycine Amidinotransferase DeficiencyDisease
Prolidase Deficiency (PD)Disease
Prolinemia Type IIDisease
Ornithine Aminotransferase Deficiency (OAT Deficiency)Disease
Hyperornithinemia-Hyperammonemia-Homocitrullinuria [HHH-syndrome]Disease
Nitric Oxide Signaling PathwaySignaling
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
AbacavirNitric Oxide may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Nitric Oxide.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Nitric Oxide.
AcarboseAcarbose may decrease the excretion rate of Nitric Oxide which could result in a higher serum level.
AcebutololThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Acebutolol.
AceclofenacAceclofenac may decrease the excretion rate of Nitric Oxide which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Nitric Oxide which could result in a higher serum level.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Nitric Oxide.
AcetaminophenThe risk or severity of methemoglobinemia can be increased when Acetaminophen is combined with Nitric Oxide.
AcetazolamideAcetazolamide may increase the excretion rate of Nitric Oxide which could result in a lower serum level and potentially a reduction in efficacy.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
GenosylGas0.98 mg/1LRespiratory (inhalation)VERO BIOTECH LLC2019-12-20Not applicableUs
InomaxInhalant800 ppmRespiratory (inhalation)Linde Healthcare Ab2001-08-01Not applicableEu
INOmaxGas0.98 mg/1LRespiratory (inhalation)INO Therapeutics1999-12-23Not applicableUs
INOmaxGas100 ppmRespiratory (inhalation)INO Therapeutics2005-11-232015-07-31Canada
InomaxInhalant400 ppmRespiratory (inhalation)Linde Healthcare Ab2001-08-01Not applicableEu
INOmaxGas800 ppmRespiratory (inhalation)INO Therapeutics2005-11-23Not applicableCanada
INOmaxGas0.123 mg/1LRespiratory (inhalation)INO Therapeutics2006-03-292006-03-29Us
InomaxInhalant800 ppmRespiratory (inhalation)Linde Healthcare Ab2001-08-01Not applicableEu
InomaxInhalant400 ppmRespiratory (inhalation)Linde Healthcare Ab2001-08-01Not applicableEu
KinoxGasRespiratory (inhalation)Airgas Usa Llc2016-05-03Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Noxivent 101Gas100 mg/1LRespiratory (inhalation)Praxair Distribution, Inc2018-10-04Not applicableUs
Noxivent 102Gas800 mg/1LRespiratory (inhalation)Praxair Distribution, Inc2018-10-04Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Nitric Oxide Nitrogen MixNitric Oxide (5 mL/1L) + Nitrogen (955 mL/1L)GasRespiratory (inhalation)Airgas Specialty Gases2010-05-01Not applicableUs

Categories

ATC Codes
R07AX01 — Nitric oxide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of inorganic compounds known as other non-metal oxides. These are inorganic compounds containing an oxygen atom of an oxidation state of -2, in which the heaviest atom bonded to the oxygen belongs to the class of 'other non-metals'.
Kingdom
Inorganic compounds
Super Class
Homogeneous non-metal compounds
Class
Other non-metal organides
Sub Class
Other non-metal oxides
Direct Parent
Other non-metal oxides
Alternative Parents
Inorganic oxides
Substituents
Inorganic oxide / Other non-metal oxide
Molecular Framework
Not Available
External Descriptors
reactive nitrogen species, reactive oxygen species, nitrogen oxide, inorganic radical (CHEBI:16480)

Chemical Identifiers

UNII
31C4KY9ESH
CAS number
10102-43-9
InChI Key
MWUXSHHQAYIFBG-UHFFFAOYSA-N
InChI
InChI=1S/NO/c1-2
IUPAC Name
nitroso
SMILES
[N]=O

References

Synthesis Reference

Stephen M. Campbell, Chen-Youn Sue, "Nitric oxide for vapor phase elimination of styrene and acrylonitrile popcorn polymer in bulk SAN production." U.S. Patent US5272231, issued November, 1968.

US5272231
General References
  1. Pacher P, Beckman JS, Liaudet L: Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007 Jan;87(1):315-424. [PubMed:17237348]
Human Metabolome Database
HMDB0003378
KEGG Drug
D00074
KEGG Compound
C00533
PubChem Compound
145068
PubChem Substance
46506897
ChemSpider
127983
RxNav
7442
ChEBI
16480
ChEMBL
CHEMBL1200689
Therapeutic Targets Database
DAP001056
PharmGKB
PA450635
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Nitric_oxide
AHFS Codes
  • 24:12.08 — Nitrates and Nitrites
MSDS
Download (52.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedDiagnosticPremature Births1
4CompletedTreatmentHeart Failure1
4CompletedTreatmentInfants / Persistent foetal circulation disorders / Respiratory Failure1
4RecruitingDiagnosticPulmonary Hypertension (PH)1
4SuspendedOtherHeart Transplant Surgery / Lung Transplant Surgery1
4WithdrawnTreatmentHypertension, Pulmonary, of Newborn, Persistent / Persistent Fetal Circulation Syndrome / Persistent Pulmonary Hypertension of Newborn (PPHN)1
3Active Not RecruitingTreatmentPulmonary Arterial Hypertension (PAH)2
3CompletedDiagnosticCardiomyopathy / Congenital Heart Disease With Pulmonary Hypertension / Idiopathic Pulmonary Arterial Hypertension1
3CompletedPreventionChronic Lung Disease of Prematurity / Chronic Lung Diseases1
3CompletedPreventionPrematurity, Respiratory Distress Syndrome,Hypoxemia1

Pharmacoeconomics

Manufacturers
  • Ino therapeutics inc
Packagers
  • Ino Therapeutics Inc.
  • Pulmonox Gas Corporation
Dosage Forms
FormRouteStrength
GasRespiratory (inhalation)0.123 mg/1L
GasRespiratory (inhalation)0.98 mg/1L
GasRespiratory (inhalation)100 ppm
GasRespiratory (inhalation)800 ppm
InhalantRespiratory (inhalation)400 ppm
InhalantRespiratory (inhalation)800 ppm
GasRespiratory (inhalation)
GasRespiratory (inhalation)
GasRespiratory (inhalation)100 mg/1L
GasRespiratory (inhalation)800 mg/1L
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5485827No1996-01-232013-01-23Us
CA2186892No2007-11-272015-04-03Canada
US5732693Yes1998-03-312017-06-13Us
US5752504Yes1998-05-192017-06-13Us
US8282966Yes2012-10-092029-12-30Us
US8291904Yes2012-10-232031-07-06Us
US8293284Yes2012-10-232029-12-30Us
US8431163Yes2013-04-302029-12-30Us
US8776794Yes2014-07-152031-07-06Us
US8776795Yes2014-07-152031-07-06Us
US8573210Yes2013-11-052031-07-06Us
US8795741Yes2014-08-052029-12-30Us
US8846112Yes2014-09-302029-12-30Us
US6125846Yes2000-10-032017-11-16Us
US9265911Yes2016-02-232031-07-06Us
US9295802Yes2016-03-292031-07-06Us
US9279794Yes2016-03-082034-08-19Us
US8573209Yes2013-11-052031-07-06Us
US9408993Yes2016-08-092031-07-06Us
US9770570Yes2017-09-262036-11-03Us
US9604028No2009-08-132029-08-13Us
US10213572No2016-02-122036-02-12Us
US7618594No2006-10-172026-10-17Us
US7560076No2007-04-212027-04-21Us
US6758214No2002-02-232022-02-23Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)-163.6 °CPhysProp
boiling point (°C)-151.7 °CPhysProp
water solubility9.49E+004 mg/LNot Available
logP0Not Available
Predicted Properties
PropertyValueSource
logP-0.35ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity2.89 m3·mol-1ChemAxon
Polarizability1.69 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9968
Blood Brain Barrier+0.9785
Caco-2 permeable+0.6149
P-glycoprotein substrateNon-substrate0.9034
P-glycoprotein inhibitor INon-inhibitor0.957
P-glycoprotein inhibitor IINon-inhibitor0.9892
Renal organic cation transporterNon-inhibitor0.8973
CYP450 2C9 substrateNon-substrate0.8884
CYP450 2D6 substrateNon-substrate0.888
CYP450 3A4 substrateNon-substrate0.7535
CYP450 1A2 substrateNon-inhibitor0.7402
CYP450 2C9 inhibitorNon-inhibitor0.9383
CYP450 2D6 inhibitorNon-inhibitor0.896
CYP450 2C19 inhibitorNon-inhibitor0.8796
CYP450 3A4 inhibitorNon-inhibitor0.9754
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8945
Ames testAMES toxic0.5342
CarcinogenicityCarcinogens 0.8336
BiodegradationReady biodegradable0.9371
Rat acute toxicity2.5108 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8524
hERG inhibition (predictor II)Non-inhibitor0.9756
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (6.86 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-9000000000-8a2dd9da1fc114d013b3
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-9000000000-8a2dd9da1fc114d013b3
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-9000000000-8a2dd9da1fc114d013b3
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9000000000-e998110984a05853a05d
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9000000000-e998110984a05853a05d
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9000000000-e998110984a05853a05d

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
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
References
  1. Moncada S, Palmer RM, Higgs EA: Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109-42. [PubMed:1852778]
  2. Mancuso C, Navarra P, Preziosi P: Roles of nitric oxide, carbon monoxide, and hydrogen sulfide in the regulation of the hypothalamic-pituitary-adrenal axis. J Neurochem. 2010 May;113(3):563-75. doi: 10.1111/j.1471-4159.2010.06606.x. Epub 2010 Jan 20. [PubMed:20089135]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
Gene Name
MT1A
Uniprot ID
P04731
Uniprot Name
Metallothionein-1A
Molecular Weight
6120.19 Da
References
  1. Aravindakumar CT, Ceulemans J, De Ley M: Nitric oxide induces Zn2+ release from metallothionein by destroying zinc-sulphur clusters without concomitant formation of S-nitrosothiol. Biochem J. 1999 Nov 15;344 Pt 1:253-8. [PubMed:10548558]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Tryptophan 2,3-dioxygenase activity
Specific Function
Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway (PubMed:17671174). Involved in the peripheral immune tolerance, cont...
Gene Name
IDO1
Uniprot ID
P14902
Uniprot Name
Indoleamine 2,3-dioxygenase 1
Molecular Weight
45325.89 Da
References
  1. Samelson-Jones BJ, Yeh SR: Interactions between nitric oxide and indoleamine 2,3-dioxygenase. Biochemistry. 2006 Jul 18;45(28):8527-38. [PubMed:16834326]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Electron carrier activity
Specific Function
Not Available
Gene Name
ALDH2
Uniprot ID
P05091
Uniprot Name
Aldehyde dehydrogenase, mitochondrial
Molecular Weight
56380.93 Da
References
  1. Moon KH, Kim BJ, Song BJ: Inhibition of mitochondrial aldehyde dehydrogenase by nitric oxide-mediated S-nitrosylation. FEBS Lett. 2005 Nov 7;579(27):6115-20. Epub 2005 Oct 11. [PubMed:16242127]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Nakano R, Sato H, Watanabe A, Ito O, Shimizu T: Conserved Glu318 at the cytochrome P450 1A2 distal site is crucial in the nitric oxide complex stability. J Biol Chem. 1996 Apr 12;271(15):8570-4. [PubMed:8621484]
  2. Mulero-Navarro S, Santiago-Josefat B, Pozo-Guisado E, Merino JM, Fernandez-Salguero PM: Down-regulation of CYP1A2 induction during the maturation of mouse cerebellar granule cells in culture: role of nitric oxide accumulation. Eur J Neurosci. 2003 Oct;18(8):2265-72. [PubMed:14622187]
  3. Donato MT, Guillen MI, Jover R, Castell JV, Gomez-Lechon MJ: Nitric oxide-mediated inhibition of cytochrome P450 by interferon-gamma in human hepatocytes. J Pharmacol Exp Ther. 1997 Apr;281(1):484-90. [PubMed:9103535]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Aitken AE, Lee CM, Morgan ET: Roles of nitric oxide in inflammatory downregulation of human cytochromes P450. Free Radic Biol Med. 2008 Mar 15;44(6):1161-8. doi: 10.1016/j.freeradbiomed.2007.12.010. Epub 2007 Dec 23. [PubMed:18206661]
  2. Lee CM, Tripathi S, Morgan ET: Nitric oxide-regulated proteolysis of human CYP2B6 via the ubiquitin-proteasome system. Free Radic Biol Med. 2017 Jul;108:478-486. doi: 10.1016/j.freeradbiomed.2017.04.015. Epub 2017 Apr 17. [PubMed:28427998]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Watabe M, Isogai Y, Numazawa S, Yoshida T: Role of c-Myc in nitric oxide-mediated suppression of cytochrome P450 3A4. Life Sci. 2003 Nov 21;74(1):99-108. [PubMed:14575816]

Drug created on June 13, 2005 07:24 / Updated on August 05, 2020 23:35

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