Carbon monoxide

Identification

Summary

Carbon monoxide is a gas used as a marker of respiratory status in spirometry tests.

Generic Name

Carbon monoxide

DrugBank Accession Number

DB11588

Background

Carbon monoxide (CO) is a colorless, odorless, and tasteless gas that has a slightly lower density than air. It is toxic to hemoglobin utilizing animals (including humans), when encountered in concentrations above about 35 ppm, although it is also formed in normal animal metabolism in low quantities, and is thought to have some normal biological/homeostatic functions ¹⁰. Carbon monoxide (CO), is a ubiquitous environmental product of organic combustion, which is also formed endogenously in the human body, as the byproduct of heme metabolism ⁸. Exhaled CO (eCO), similar to exhaled nitric oxide (eNO), has been evaluated as a candidate breath biomarker of pathophysiological states, including smoking status, and inflammatory diseases of the lung and other organs. Exhalation of corbon monoxide values have been studied as potential indicators of inflammation in asthma, stable COPD and exacerbations, cystic fibrosis, lung cancer, and during surgery or critical care ¹⁰.

A test of the diffusing capacity of the lungs for carbon monoxide (DLCO), is one of the most clinically valuable tests of lung function testing. The technique was first described 100 years ago, and applied to clinical practice many years after. The DLCO measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries. The DLCO test is both convenient and simple for the patient to undergo. The ten seconds of breath-holding required for the DLCO maneuver is easier for most patients to perform than the forced exhalation required for other respiratory tests ²⁸.

Carbon monoxide is presently used in small amounts in low oxygen modified atmosphere packaging systems (MAP) for fresh meat to stabilize and maintain natural meat color. This use of CO has been generally recognized as safe (GRAS) in several packaging applications for fresh meat products. Since 2002, FDA has favorably reviewed three GRAS notifications for carbon monoxide use in fresh meat packaging ¹⁵. The FDA classifies this drug as permitted as a food additive in the packaging and preparation of food products, while following the federal code of regulations ¹².

There have been several concerns voiced of over the use of carbon monoxide in food products ¹⁵, ¹⁶, ¹⁷. The European Union has banned the use of carbon monoxide as a color stabilizer in meat and fish. A December 2001 report from the European Commission's Scientific Committee on Food concluded that the gas did not pose a risk provided that food was maintained adequately cold during storage and transport to prevent the growth of microorganisms ¹⁶. In New Zealand, the use of carbon monoxide in fish preparation has been banned, as it may mask the effects of food spoilage and bacterial growth ¹⁷.

Type

Small Molecule

Groups

Approved, Investigational

Structure

Similar Structures

Weight: Average: 28.01
Monoisotopic: 27.99491462
Chemical Formula: CO

Synonyms

Carbon monoxide
carbon(II) oxide
Carboneum oxygenisatum
CO

Pharmacology

Indication

Used as a marker of respiratory status in spirometry tests ²⁸, ³¹.

Food additive for pigment fixation in meat ¹².

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Contraindications & Blackbox Warnings

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Pharmacodynamics

Carbon monoxide is used to measure the diffusing capacity for carbon monoxide (DLCO), also known as the transfer factor for carbon monoxide. It is a measure of the gas transfer from inspired gas to the circulatory system (red blood cells in particular) ²⁸. It is used in a particular pulmonary function test called "the single-breath test" ³².

DLCO, measured for clinical and research purposes almost exclusively by the single-breath method is an important and very useful pulmonary function test. It is useful in the evaluation of patients with dyspnea, obstructive lung diseases, restrictive lung diseases, and in patients with diseases of the pulmonary vasculature. The measurement of DLCO using carbon monoxide is representative of the surface area available, the volume of blood present in the pulmonary capillaries, as well as the thickness of the alveolar-capillary membrane ³².

Conditions that increase DLCO: Heart failure, erythrocythemia, alveolar hemorrhage, asthma

Conditions that decrease DLCO: emphysema, pulmonary fibrosis, pulmonary hypertension, pulmonary embolism

In addition to the above uses, carbon monoxide (CO) is increasingly being accepted in recent years as a protective molecule with important signaling capabilities in both physiological/homeostatic and pathophysiological situations. The endogenous production of CO occurs via the activity of constitutive (heme oxygenase 2) and inducible (heme oxygenase 1) heme oxygenase enzymes, which are both responsible for the breakdown of heme. Through the generation of its products, which in addition to carbon monoxide, includes the biliary pigments biliverdin, bilirubin and ferrous iron, the heme oxygenase 1 system also have an essential role in the regulation of the stress response and in cell adaptation to injury. Preclinical studies have suggested potential benefits of carbon monoxide in cardiovascular disease, inflammatory disorders, as well as organ transplantation ³.

Mechanism of action

In respiratory testing, the diffusing capacity for carbon monoxide (DLCO) is a measure of the ability of gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. The DLCO depends not only on the area and thickness of the blood-gas barrier but additionally on the volume of blood in the pulmonary capillaries. The distribution of alveolar volume and ventilation also has an impact on the measurement ²⁹.

DLCO is measured by sampling end-expiratory gas for carbon monoxide (CO) after patients inspire a small and safe amount of exogenous CO, hold their breath, and exhale. Measured DLCO is adjusted for alveolar volume (which is estimated from dilution of helium) and the patient’s hematocrit level. DLCO is reported as mL/min/mm Hg and as a percentage of a predicted value ⁹.

Carbon monoxide exerts effects on cell metabolism through both hypoxic and non-hypoxic modes of action. Both mechanisms of action are thought to be the result of the ability of carbon monoxide to bind strongly to heme and alter the function and/or metabolism of heme proteins. The binding affinity of carbon monoxide for hemoglobin is more than 200 times greater than that of oxygen for hemoglobin. The formation of carboxyhemoglobin (COHb) decreases the O2 carrying capacity of blood and disrupts the release of O2 from Hb for its use in tissues. Through similar mechanisms, carbon monoxide diminishes the O2 storage in muscle cells by binding to and displacing O2 from, myoglobin. Though all human tissues are vulnerable to carbon monoxide-induced hypoxic injury, those with the highest O2 demand are especially vulnerable, including the brain and heart ²⁶.

Most of the non-hypoxic mechanisms of action of carbon monoxide have been thought to be due to binding of carbon monoxide to heme in proteins other than Hb. The most notable targets of carbon monoxide include components of many important physiological regulatory systems, including brain and muscle oxygen storage and use(myoglobin, neuroglobin); nitric oxide cell signaling (e.g., nitric oxide synthase, guanylyl cyclase); prostaglandin cell signaling (cyclooxygenase, prostaglandin H synthase); energy metabolism and mitochondrial respiration (cytochrome c oxidase, cytochrome c, NADPH oxidase); steroid and drug metabolism (cytochrome P450); cellular redox balance and reactive oxygen species (ROS; catalase, peroxidases); and numerous transcription factors (e.g., neuronal PAS domain protein, NPAS2, implicated in regulation of circadian rhythm) ²⁶.

In meat processing, carbon monoxide reacts with myoglobin, to form carboxymyoglobin, imparting a red appearance to the meat ¹⁸.

Target	Actions	Organism
AMyoglobin	inhibitor	Humans

Absorption

Although CO is not one of the respiratory gases, the similarity of physico-chemical properties of CO and oxygen (O2) permits an extension of the findings of studies on the kinetics of transport of O2 to those of CO. The rate of formation and elimination of COHb, its concentration in blood, and its catabolism is controlled by numerous physical factors and physiological mechanisms ²³.

The absorption of carbon monoxide from the consumption treated food products is not significant. Risk of CO toxicity from the packaging process or from consumption of CO-treated meats is negligible ⁶.

Volume of distribution

Not Available

Protein binding

Binds with very high affinity to hemoglobin in humans ²⁵.

Metabolism

Not Available

Route of elimination

Not Available

Half-life

The half-life of carbon monoxide at room air temperature is 3-4 hours. 100% oxygen reduces the half-life to 30-90 minutes; hyperbaric oxygen at 2.5 atm (atmosphere units) with 100% oxygen reduces it to 15-23 minutes ²⁷.

Clearance

Not Available

Adverse Effects

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Toxicity

LD50 is 1807 ppm in rats after 4 hours of exposure ^MSDS. In humans, exposure to 4000 ppm or more in less than 1 hour leads to death ²⁰.

Carbon Monoxide Toxicity from Food Ingestion Treated with Carbon Monoxide

Very little information has been published in the literature on the consumer’s exposure to CO-packaged meat. The toxicological aspects of CO used in MAP of meat were reviewed by Sørheim et al. ⁷, and they concluded that, with up to about 0.5% of CO, no human toxicity is likely. It has been suggested that the consumption of CO-treated meat is not associated with any health risks, and meat from CO-MAP results only in negligible amounts of CO and COHb in humans ²³, ²⁴.

Mechanism of CO Toxicity

Once CO is inhaled, it binds with hemoglobin to form carboxyhemoglobin (COHb) with an affinity of 200 times greater than oxygen that leads to decreased oxygen-carrying capacity and the decreased release of oxygen to tissues, causing tissue hypoxia. Ischemia occurs with CO poisoning when there is a loss of consciousness combined with hypotension and ischemia in the arterial border areas of the brain. Besides binding to many heme-containing proteins, CO interrupts oxidative metabolism, leading to the formation of free radicals. Once hypotension and unconsciousness occur with CO poisoning, lipid peroxidation and apoptosis soon follow ².

Failure to diagnose CO poisoning may result in morbidity and mortality and allow for continued exposure to a dangerous environment. The management of CO poisoning begins with inhalation of supplemental oxygen therapy and aggressive supportive measures. Hyperbaric oxygen therapy (HBOT) accelerates the dissociation of CO from hemoglobin ¹.

The concentration, exposure time and physical activity of the individual will determine the percentage conversion of haemoglobin to carboxyhaemoglobin. The effects produced depend on the degree and duration of saturation of blood with carbon monoxide ²⁰.

Levels of Intoxication with Carbon Monoxide ²

The first symptoms of carbon monoxide exposure when carboxyhemoglobin is 15-30% are generalized, and may include: headache, dizziness, nausea, fatigue, and impaired manual dexterity. Individuals with ischemic heart disease may suffer from chest pain and decreased exercise duration at COHb levels measured from 1% - 9% ².

COHb levels between 30-70% lead to loss of consciousness and eventually death ².

Long-term Effects ²

Following the resolution of the acute symptoms, there may be a lucid interval from 2-40 days before the development of delayed neurologic sequelae (DNS). Diffuse brain demyelination combined with lethargy, behavioral changes, memory loss, and parkinsonian features may occur. 75% of patients with DNS recover within 1 year. Neuropsychologic abnormalities with chronic CO exposure are found even when magnetic resonance imaging (MRI) and magnetic resonance spectroscopy findings are normal. White-matter damage in the centrum semiovale and periventricular area of the brain, and abnormalities in the globus pallidus, are most commonly observed on MRI following CO toxicity. Though less common, toxic or ischemic peripheral neuropathies are associated with high levels of CO exposure in humans. The basis for the management of CO poisoning is 100% hyperbaric oxygen therapy using a tight-fitting mask for at least 6 hours. The indications for treatment with hyperbaric oxygen to decrease the half-life of COHb remain controversial ².

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.
Not Available
Food Interactions: No interactions found.

Products

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Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Carbon Monox, Helium, Oxygen, Nitrogen L.D.M.	Carbon monoxide (0.3 %) + Helium (10.5 %) + Nitrogen (67.7 %) + Oxygen (21.5 %)	Gas	Respiratory (inhalation)	Praxair, Inc.	1993-12-31	Not applicable
Carbon Monoxide, Compressed Air Medical G.M.	Carbon monoxide (0.3 %) + Medical air (99.7 %)	Gas	Respiratory (inhalation)	Praxair, Inc.	1993-12-31	Not applicable
Co-HE-O2-N2 Mixture	Carbon monoxide (0.3 %) + Helium (10.0 %) + Nitrogen (68.7 %) + Oxygen (21.0 %)	Gas	Respiratory (inhalation)	Messer Canada Inc.	1995-12-31	Not applicable
Co-NE-O2-N2 Mixture	Carbon monoxide (0.3 % v/v) + Neon (0.5 % v/v) + Nitrogen (78.2 % v/v) + Oxygen (21 % v/v)	Gas	Respiratory (inhalation)	Messer Canada Inc.	1995-12-31	Not applicable
iCOmas 0,3 % / 0,3 % / 0,3 % Gas zur medizinischen Anwendung, druckverdichtet	Carbon monoxide (0.3 %) + Acetylene (0.3 %) + Methane (0.3 %)	Gas	Respiratory (inhalation)	Linde Sverige Ab	2018-07-05	Not applicable
iCOmix 0,28 % / 9,3 % Gas zur medizinischen Anwendung, druckverdichtet	Carbon monoxide (0.28 %) + Helium (9.3 %)	Gas	Respiratory (inhalation)	Linde Sverige Ab	2018-07-05	Not applicable
Lung Diffusion Test Mix No Ne Co	Carbon monoxide (0.3 %) + Neon (0.5 %) + Nitrogen (78.2 %) + Oxygen (21 %)	Gas	Respiratory (inhalation)	Praxair, Inc.	1968-12-31	Not applicable
Lung Diffusion Test Mix Nohco	Carbon monoxide (.3 %) + Helium (10 %) + Nitrogen (68.7 %) + Oxygen (21 %)	Gas	Respiratory (inhalation)	Liquid Carbonic Inc.	1968-12-31	1998-06-09
Lung Diffusion Test Mixture	Carbon monoxide (.5 %) + Helium (15 %) + Nitrogen (74 %) + Oxygen (23 %)	Gas	Respiratory (inhalation)	Matheson Gas Products Canada Inc.	1982-12-31	1997-12-24
Lung Diffusion Test Mixture	Carbon monoxide (.4 %) + Medical air (99.99 %)	Gas	Respiratory (inhalation)	Matheson Gas Products Canada Inc.	1982-12-31	1997-12-24

Chemical Identifiers

UNII: 7U1EE4V452
CAS number: 630-08-0
InChI Key: UGFAIRIUMAVXCW-UHFFFAOYSA-N
InChI: InChI=1S/CO/c1-2
IUPAC Name
SMILES

References

General References

Kao LW, Nanagas KA: Carbon monoxide poisoning. Med Clin North Am. 2005 Nov;89(6):1161-94. doi: 10.1016/j.mcna.2005.06.007. [Article]
Bleecker ML: Carbon monoxide intoxication. Handb Clin Neurol. 2015;131:191-203. doi: 10.1016/B978-0-444-62627-1.00024-X. [Article]
Motterlini R, Otterbein LE: The therapeutic potential of carbon monoxide. Nat Rev Drug Discov. 2010 Sep;9(9):728-43. doi: 10.1038/nrd3228. [Article]
Nikolic I, Saksida T, Mangano K, Vujicic M, Stojanovic I, Nicoletti F, Stosic-Grujicic S: Pharmacological application of carbon monoxide ameliorates islet-directed autoimmunity in mice via anti-inflammatory and anti-apoptotic effects. Diabetologia. 2014 May;57(5):980-90. doi: 10.1007/s00125-014-3170-7. Epub 2014 Feb 2. [Article]
Rochette L, Cottin Y, Zeller M, Vergely C: Carbon monoxide: mechanisms of action and potential clinical implications. Pharmacol Ther. 2013 Feb;137(2):133-52. doi: 10.1016/j.pharmthera.2012.09.007. Epub 2012 Sep 29. [Article]
Djenane D, Roncales P: Carbon Monoxide in Meat and Fish Packaging: Advantages and Limits. Foods. 2018 Jan 23;7(2). pii: foods7020012. doi: 10.3390/foods7020012. [Article]
Sorheim O, Nissen H, Nesbakken T: The storage life of beef and pork packaged in an atmosphere with low carbon monoxide and high carbon dioxide. Meat Sci. 1999 Jun;52(2):157-64. [Article]
Ryter SW, Choi AM: Carbon monoxide in exhaled breath testing and therapeutics. J Breath Res. 2013 Mar;7(1):017111. doi: 10.1088/1752-7155/7/1/017111. Epub 2013 Feb 27. [Article]
Hu HJ, Sun Q, Ye ZH, Sun XJ: Characteristics of exogenous carbon monoxide deliveries. Med Gas Res. 2016 Jul 11;6(2):96-101. doi: 10.4103/2045-9912.184719. eCollection 2016 Apr-Jun. [Article]
CARBON MONOXIDE [Link]
Therapeutic Applications of Carbon Monoxide [Link]
FDA Federal Code of Regulation Document [Link]
Diverse Pharmacological Effects of Carbon Monoxide-Releasing Molecules [Link]
Carbon Monoxide: Endogenous Production, Physiological Functions, and Pharmacological Applications [Link]
Regulatory Status of Carbon Monoxide for Meat Packaging [Link]
FDA Is Urged to Ban Carbon-Monoxide-Treated Meat [Link]
NZ document, carbon monoxide in fish [Link]
Subscribe to our FREE newsletter Subscribe FDA asked to rescind use of carbon monoxide for meats [Link]
Modified Atmosphere Packaging (MAP): Microbial Control and Quality [Link]
Afrox Carbon Monoxide MSDS [Link]
Myoglobin Chemistry and Meat Color [Link]
WHO document, toxokinetics of CO [Link]
Pharmacokinetics and Mechanisms of Action of Carbon Monoxide [Link]
METMYOGLOBIN REDUCTION IN BEEF SYSTEMS AS AFFECTED BY AEROBIC, ANAEROBIC AND CARBON MONOXIDE‐CONTAINING ENVIRONMENTS [Link]
The binding of carbon monoxide to hemoglobin [Link]
CDC toxicological Profile for Carbon Monoxide [Link]
Carbon Monoxide Toxicity [Link]
Diffusing capacity for carbon monoxide [Link]
Merck Manuals, Diffusing Lung Capacity [Link]
Praxair website [Link]
The carbon monoxide diffusing capacity [File]
2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung [File]

External Links

Human Metabolome Database: HMDB0001361
KEGG Drug: D09706
KEGG Compound: C00237
PubChem Compound: 281
PubChem Substance: 347827995
ChemSpider: 275
RxNav: 2037
ChEBI: 17245
ChEMBL: CHEMBL1231840
PDBe Ligand: CMO
Wikipedia: Carbon_monoxide

PDB Entries

1a6g / 1a9w / 1abs / 1aj9 / 1ajg / 1ajh / 1bbb / 1bzr / 1cbm / 1cg8 …

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MSDS

Download (144 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
2	Active Not Recruiting	Treatment	Acute Respiratory Distress Syndrome (ARDS)	1
2	Completed	Treatment	Chronic Obstructive Pulmonary Disease (COPD)	1
2	Completed	Treatment	Idiopathic Pulmonary Fibrosis (IPF)	1
2	Terminated	Treatment	Ileus	1
2	Withdrawn	Basic Science	Kidney Transplantation	1
1	Completed	Other	Endothelial Dysfunction	1
1	Completed	Treatment	Acute Respiratory Distress Syndrome (ARDS)	1
1	Completed	Treatment	Respiratory Distress Syndrome, Adult	1
1	Recruiting	Treatment	Acute Respiratory Distress Syndrome (ARDS) / Sepsis	1
1	Terminated	Other	Endothelial Dysfunction / Smoking	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Gas	Respiratory (inhalation)

Prices

Not Available

Patents

Not Available

Properties

State

Gas

Experimental Properties

Property	Value	Source
boiling point (°C)	-191.5	MSDS

Predicted Properties

Property	Value	Source
Water Solubility	6.37 mg/mL	ALOGPS
logP	-0.06	ALOGPS
logS	-1.1	ALOGPS
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	0	Chemaxon
Hydrogen Donor Count	0	Chemaxon
Polar Surface Area	0 Å²	Chemaxon
Rotatable Bond Count	0	Chemaxon
Refractivity	26.23 m³·mol^-1	Chemaxon
Polarizability	1.94 Å³	Chemaxon
Number of Rings	0	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	Yes	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Mass Spectrum (Electron Ionization)	MS	splash10-004i-9000000000-dfbb2bd73fc3d527a340
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Targets

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Details1. Myoglobin

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Oxygen transporter activity
Specific Function: Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles.
Gene Name: MB
Uniprot ID: P02144
Uniprot Name: Myoglobin
Molecular Weight: 17183.725 Da

References

Djenane D, Roncales P: Carbon Monoxide in Meat and Fish Packaging: Advantages and Limits. Foods. 2018 Jan 23;7(2). pii: foods7020012. doi: 10.3390/foods7020012. [Article]
Blumenthal I: Carbon monoxide poisoning. J R Soc Med. 2001 Jun;94(6):270-2. doi: 10.1177/014107680109400604. [Article]

Drug created at April 28, 2016 18:59 / Updated at October 21, 2021 04:40

Carbon monoxide

Identification

Structure for Carbon monoxide (DB11588)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Targets

References