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Identification
NameNitric Oxide
Accession NumberDB00435  (APRD01142)
TypeSmall Molecule
GroupsApproved
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.

Structure
Thumb
Synonyms
(.)NO
(NO)(.)
[NO]
EDRF
endothelium-derived relaxing factor
Mononitrogen monoxide
Monoxido de nitrogeno
Monoxyde d'azote
Nitric oxide
nitrogen monooxide
Nitrogen monoxide
Nitrosyl
NO
NO(.)
Oxido de nitrogeno(ii)
Oxido nitrico
Oxyde azotique
Oxyde nitrique
Stickstoff(ii)-oxid
Stickstoffmonoxid
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Inomaxgas.98 mg/Lrespiratory (inhalation)INO Therapeutics1999-12-23Not applicableUs
Inomaxgas100 ppminhalationINO Therapeutics2005-11-232015-07-31Canada
Inomaxgas800 ppminhalationINO Therapeutics2005-11-23Not applicableCanada
Inomaxgas.123 mg/Lrespiratory (inhalation)INO Therapeutics1999-12-232015-12-29Us
Kinoxgas100 ppminhalationAir Liquide Healthcare America Corporation2016-05-03Not applicableCanada
Kinoxgas800 ppminhalationAir Liquide Healthcare America Corporation2016-05-03Not applicableCanada
Noxiventgas800 ppminhalationPraxair Canada Inc2016-03-10Not applicableCanada
Noxiventgas100 ppminhalationPraxair Canada Inc2016-03-10Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Nitric Oxide Nitrogen MixAirgas Specialty Gases
SaltsNot Available
Categories
UNII31C4KY9ESH
CAS number10102-43-9
WeightAverage: 30.0061
Monoisotopic: 29.997988627
Chemical FormulaNO
InChI KeyInChIKey=MWUXSHHQAYIFBG-UHFFFAOYSA-N
InChI
InChI=1S/NO/c1-2
IUPAC Name
nitroso
SMILES
[N]=O
Taxonomy
DescriptionThis compound belongs to the class of inorganic compounds known as homogeneous other non-metal compounds. These are inorganic non-metallic compounds in which the largest atom belongs to the class of 'other nonmetals'.
KingdomInorganic compounds
Super ClassHomogeneous non-metal compounds
ClassHomogeneous other non-metal compounds
Sub ClassNot Available
Direct ParentHomogeneous other non-metal compounds
Alternative Parents
Substituents
  • Homogeneous other non metal
  • Inorganic oxide
  • Acyclic compound
Molecular FrameworkAcyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of term and near-term (>34 weeks) neonates with hypoxic respiratory failure
PharmacodynamicsPersistent 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 actionNitric 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.
Related Articles
AbsorptionNitric oxide is absorbed systemically after inhalation.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

via pulmonary capillary bed

Route of eliminationNitrate has been identified as the predominant nitric oxide metabolite excreted in the urine, accounting for >70% of the nitric oxide dose inhaled.
Half life2–6 seconds
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Ornithine Aminotransferase Deficiency (OAT Deficiency)DiseaseSMP00363
Prolidase Deficiency (PD)DiseaseSMP00207
Arginine and Proline MetabolismMetabolicSMP00020
Prolinemia Type IIDiseaseSMP00208
Hyperprolinemia Type IDiseaseSMP00361
Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)DiseaseSMP00188
Hyperprolinemia Type IIDiseaseSMP00360
Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)DiseaseSMP00362
Creatine deficiency, guanidinoacetate methyltransferase deficiencyDiseaseSMP00504
Hyperornithinemia with gyrate atrophy (HOGA)DiseaseSMP00505
Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome]DiseaseSMP00506
L-arginine:glycine amidinotransferase deficiencyDiseaseSMP00507
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Ino therapeutics inc
Packagers
Dosage forms
FormRouteStrength
Gasinhalation100 ppm
Gasinhalation800 ppm
Gasrespiratory (inhalation).123 mg/L
Gasrespiratory (inhalation).98 mg/L
Gasrespiratory (inhalation)
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2186892 No2007-11-272015-04-03Canada
US5485827 No1993-01-232013-01-23Us
US5732693 Yes1997-06-132017-06-13Us
US5752504 Yes1997-06-132017-06-13Us
US6125846 Yes1997-11-162017-11-16Us
US8282966 Yes2009-12-302029-12-30Us
US8291904 Yes2011-07-062031-07-06Us
US8293284 Yes2009-12-302029-12-30Us
US8431163 Yes2009-12-302029-12-30Us
US8573209 Yes2011-07-062031-07-06Us
US8573210 Yes2011-07-062031-07-06Us
US8776794 Yes2011-07-062031-07-06Us
US8776795 Yes2011-07-062031-07-06Us
US8795741 Yes2009-12-302029-12-30Us
US8846112 Yes2009-12-302029-12-30Us
US9265911 Yes2011-07-062031-07-06Us
US9279794 Yes2014-08-192034-08-19Us
US9295802 Yes2011-07-062031-07-06Us
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point-163.6 °CPhysProp
boiling point-151.7 °CPhysProp
water solubility9.49E+004 mg/LNot Available
logP0Not Available
Predicted Properties
PropertyValueSource
logP-0.35ChemAxon
pKa (Strongest Basic)-2.9ChemAxon
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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (6.86 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-9000000000-8a2dd9da1fc114d013b3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-9000000000-8a2dd9da1fc114d013b3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9000000000-8a2dd9da1fc114d013b3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-9000000000-e998110984a05853a05dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-9000000000-e998110984a05853a05dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9000000000-e998110984a05853a05dView in MoNA
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 ]
External Links
ATC CodesR07AX01
AHFS Codes
  • 24:12.08
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (52.8 KB)
Interactions
Drug Interactions
Drug
AcetaminophenThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Acetaminophen.
Amyl NitriteThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Amyl Nitrite.
BenzocaineThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Benzocaine.
ButalbitalThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Butalbital.
CelecoxibThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Celecoxib.
ChloroquineThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Chloroquine.
DapsoneThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Dapsone.
FlutamideThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Flutamide.
IsosorbideThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Isosorbide.
Isosorbide DinitrateThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Isosorbide Dinitrate.
Isosorbide MononitrateThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Isosorbide Mononitrate.
LidocaineThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Lidocaine.
MafenideThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Mafenide.
MetoclopramideThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Metoclopramide.
NitrofurantoinThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Nitrofurantoin.
NitroglycerinThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Nitroglycerin.
NitroprussideThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Nitroprusside.
PhenazopyridineThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Phenazopyridine.
PhenobarbitalThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Phenobarbital.
PhenytoinThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Phenytoin.
PrilocaineThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Prilocaine.
PrimaquineThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Primaquine.
QuinineThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Quinine.
Sodium NitriteThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Sodium Nitrite.
SulfadiazineThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Sulfadiazine.
ZopicloneThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Zopiclone.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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
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 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Electron carrier activity
Specific Function:
Not Available
Gene Name:
ALDH2
Uniprot ID:
P05091
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
Human
Pharmacological action
unknown
Actions
substrate
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
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 ]
Kind
Protein
Organism
Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
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 ]
Kind
Protein
Organism
Human
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on July 25, 2016 03:10