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Identification
- Brand Names
- Kenalog
- Generic Name
- Ammonia
- DrugBank Accession Number
- DB11118
- Background
Ammonia is a naturally-occurring compound with a chemical formula NH3 and structure of trigonal pyramidal geometry. It is a colorless gas with a pungent smell, and become NH4, or ammonium ion, when in water. Although ammonia is used as a food additive in the anhydrous form and serves as a starting material in pharmaceutical and commercial products, it is caustic and hazardous when concentrated. Ammonia gas has been used in the clinical setting as a respiratory stimulant to prevent fainting. The radiolabelled form of ammonia, ammonia N 13, is intravenously administered as a radioactive diagnostic agent for Positron Emission Tomography (PET) imaging of the myocardium to evaluate myocardial perfusion. Ammonia is a natural byproduct of biological and chemical reactions, including decomposition of organic matter, including plants, animals, and animal wastes. It is present in normally present in all tissues constituting a metabolic pool, where it is mostly taken up by glutamic acid and take part in transamination and other reactions, including the synthesis of protein by the Krebs-Hanseleit cycle in the liver 5. It is proposed that human adults produce about 1000 mmol of ammonia daily, most of which undergoes excretion in the urine.
- Type
- Small Molecule
- Groups
- Approved
- Synonyms
- Not Available
Pharmacology
- Indication
- Indicated for use as a smelling salt to treat or prevent fainting.
- (when radiolabelled) Indicated for diagnostic PET imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease Label.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Skin irritation ••• ••• •••• •••••• Prophylaxis of Faintness/fainting ••• ••• ••••••• - Contraindications & Blackbox Warnings
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As a gas, ammonia is a natural byproduct and respiratory stimulant. Its renal metabolism plays a role in whole body acid-base balance.
- Mechanism of action
Renal excretion and metabolism of ammonia is critical in regulation of acid-base balance by generating bicarbonate ions and promoting renal net acid excretion, both under basal conditions and in response to acid-base disturbances 4. There is evidence that acute ammonia exposure activates NMDA receptor signalling pathways, and high concentrations of ammonia resulting from urea cycle enzyme deficiencies are associated with changes in astrocyte morphology due to glutamine accumulation, changes in the expression of key astrocyte proteins, and increased concentrations of neuroactive L-tryptophan metabolites 2.
- Absorption
Ammonia can be absorbed via oral or inhalation route. Inhales ammonia is temporarily dissolved in the mucus of the upper respiratory tract, however the majority of the gas is released back into the air via expiration 5. In healthy male subjects under exposure to 500 ppm ammonia for 10-27 minutes, about 70-80% of total inspired ammonia was expired 5. In extrahepatic tissues such as the intestine, ammonia is incorporated into nontoxic glutamine and released into blood, where it is transported to the liver for ureagenesis 5.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Healthy hepatocytes detoxify ammonia where hepatic glutaminase, glutamine synthetase and the urea cycle enzymes act as major enzymes for ammonia metabolism. Ammonia is converted to urea in the liver and other tissues. Glutaminase and glutamine synthetase catalyze the condensation of ammonia with glutamate to glutamine, which is a common nontoxic carrier of ammonia 3. In case of hepatic dysfunction or impairment, detoxification capacity decreases and may cause severe pathologies from hyperammonemia, such as hepatic encephalopathy 5.
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- Route of elimination
It is mainly excreted through expired air or renal elimination 5.
- Half-life
In normal rat brain, blood-derived ammonia was rapidly converted to glutamine, indicating very short half-life of less than 3 seconds 5.
- Clearance
Not Available
- Adverse Effects
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LC50 via inhalation in rat is 7338 ppm/1h MSDS. High exposure to ammonia can cause pulmonary edema, which may be life-threatening. Exposure can cause headache, loss of sense of smell, nausea, and vomiting. While mammals has various mechanisms to detoxify and excrete ammonia from the body, death has been reported after an exposure to 10,000 ppm for an unknown duration. Bradycardia was seen at 2,500 ppm, and hypertension and cardiac arrhythmias leading to cardiovascular collapse followed acute exposures to concentrations exceeding 5,000 ppm 5.
- 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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Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ammonia Inhalant 0.045 g/0.3mL Respiratory (inhalation) Physicians Total Care, Inc. 2012-08-17 2013-01-15 US 
Ammonia Inhalants Inhalant 0.045 g/0.3mL Respiratory (inhalation) Sina Health Inc 1976-02-14 Not applicable US Ammonia Inhalants Inhalant 0.045 g/0.3mL Respiratory (inhalation) A-S Medication Solutions 1976-02-14 Not applicable US Ammonia Inhalants Inhalant 0.045 g/0.3mL Respiratory (inhalation) XGen Pharmaceuticals DJB, Inc. 1976-02-14 2020-09-25 US Ammonia Inhalants Inhalant 0.045 g/0.3mL Respiratory (inhalation) Remedy Repack 2015-03-24 2017-03-21 US - Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image 4010 First Aid Kit Kit 0.045 g/0.3mL Topical Honeywell Safety Products USA, Inc. 2018-10-14 2019-10-18 US After Bite Liquid 3.61% Liquid 3.61 % Topical Tender Corporation 1990-12-31 1998-09-11 Canada 
After Bite Outdoor Liquid 3.5 g/100g Topical Tender Corporation 2014-11-25 2016-11-01 US After Bite The Itch Eraser KIDS Liquid 3.5 g/100g Topical Tender Corporation 2014-11-25 2014-11-25 US After Bite The Itch Eraser Xtra Liquid 3.5 g/100g Topical Tender Corporation 2014-11-25 2014-11-26 US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image 4032 First Aid Kit Ammonia (0.045 g/0.3mL) + Acetylsalicylic acid (325 mg/1) + Bacitracin zinc (400 [iU]/1g) + Benzalkonium chloride (1.3 mg/1mL) + Lidocaine hydrochloride (24.64 mg/1mL) + Neomycin sulfate (3.5 mg/1g) + Polymyxin B sulfate (5000 [iU]/1g) + Water (98.6 mL/100mL) Inhalant; Kit; Liquid; Ointment; Spray; Tablet Ophthalmic; Oral; Respiratory (inhalation); Topical Honeywell Safety Products USA, Inc 2018-10-18 Not applicable US 4076 First Aid Kit Ammonia (0.045 g/0.3mL) + Acetaminophen (325 mg/1) + Benzalkonium chloride (0.13 g/100g) + Benzalkonium chloride (1.3 mg/1mL) + Ethanol (0.5 mL/1mL) + Lidocaine hydrochloride (20 mg/1mL) + Lidocaine hydrochloride (0.5 g/100g) + Neomycin sulfate (3.5 mg/1g) + Water (98.6 mL/100mL) Kit Topical Honeywell Safety Products USA, Inc 2018-10-18 Not applicable US 4121 First Aid Kit Ammonia (0.045 g/0.3mL) + Benzalkonium chloride (1.3 mg/1mL) + Benzalkonium chloride (0.13 g/100g) + Lidocaine hydrochloride (0.5 g/100g) + Water (98.6 mL/100mL) Kit Ophthalmic; Respiratory (inhalation); Topical Honeywell Safety Products USA, Inc. 2019-01-24 2019-10-18 US 4125 First Aid Kit Ammonia (0.045 g/0.3mL) + Bacitracin zinc (400 [iU]/1g) + Benzalkonium chloride (1.3 mg/1mL) + Benzethonium chloride (0.2 g/100g) + Benzethonium chloride (0.2 g/100g) + Benzocaine (10 g/100g) + Benzocaine (10 g/100g) + Isopropyl alcohol (0.7 mL/1mL) + Menthol (0.33 g/100g) + Neomycin sulfate (3.5 mg/1g) + Polymyxin B sulfate (5000 [iU]/1g) + Water (98.6 mL/100mL) Inhalant; Kit; Liquid; Ointment; Spray; Swab Ophthalmic; Respiratory (inhalation); Topical Honeywell Safety Products USA, Inc 2018-10-18 Not applicable US 4129 First Aid Kit Ammonia (0.045 g/0.3mL) + Benzalkonium chloride (1.3 mg/1mL) + Benzethonium chloride (0.2 g/100g) + Benzocaine (20 g/100g) + Ethanol (0.5 mL/1mL) + Hydrocortisone acetate (1 g/100g) + Hydrocortisone acetate (1 g/100g) + Isopropyl alcohol (0.7 mL/1mL) + Lidocaine hydrochloride (20 mg/1mL) + Povidone-iodine (10 mg/1mL) Kit Respiratory (inhalation); Topical Honeywell Safety Products USA, Inc 2018-10-18 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image 4010 First Aid Kit Ammonia (0.045 g/0.3mL) Kit Topical Honeywell Safety Products USA, Inc. 2018-10-14 2019-10-18 US 4032 First Aid Kit Ammonia (0.045 g/0.3mL) + Acetylsalicylic acid (325 mg/1) + Bacitracin zinc (400 [iU]/1g) + Benzalkonium chloride (1.3 mg/1mL) + Lidocaine hydrochloride (24.64 mg/1mL) + Neomycin sulfate (3.5 mg/1g) + Polymyxin B sulfate (5000 [iU]/1g) + Water (98.6 mL/100mL) Inhalant; Kit; Liquid; Ointment; Spray; Tablet Ophthalmic; Oral; Respiratory (inhalation); Topical Honeywell Safety Products USA, Inc 2018-10-18 Not applicable US 4076 First Aid Kit Ammonia (0.045 g/0.3mL) + Acetaminophen (325 mg/1) + Benzalkonium chloride (0.13 g/100g) + Benzalkonium chloride (1.3 mg/1mL) + Ethanol (0.5 mL/1mL) + Lidocaine hydrochloride (20 mg/1mL) + Lidocaine hydrochloride (0.5 g/100g) + Neomycin sulfate (3.5 mg/1g) + Water (98.6 mL/100mL) Kit Topical Honeywell Safety Products USA, Inc 2018-10-18 Not applicable US 4121 First Aid Kit Ammonia (0.045 g/0.3mL) + Benzalkonium chloride (1.3 mg/1mL) + Benzalkonium chloride (0.13 g/100g) + Lidocaine hydrochloride (0.5 g/100g) + Water (98.6 mL/100mL) Kit Ophthalmic; Respiratory (inhalation); Topical Honeywell Safety Products USA, Inc. 2019-01-24 2019-10-18 US 4125 First Aid Kit Ammonia (0.045 g/0.3mL) + Bacitracin zinc (400 [iU]/1g) + Benzalkonium chloride (1.3 mg/1mL) + Benzethonium chloride (0.2 g/100g) + Benzethonium chloride (0.2 g/100g) + Benzocaine (10 g/100g) + Benzocaine (10 g/100g) + Isopropyl alcohol (0.7 mL/1mL) + Menthol (0.33 g/100g) + Neomycin sulfate (3.5 mg/1g) + Polymyxin B sulfate (5000 [iU]/1g) + Water (98.6 mL/100mL) Inhalant; Kit; Liquid; Ointment; Spray; Swab Ophthalmic; Respiratory (inhalation); Topical Honeywell Safety Products USA, Inc 2018-10-18 Not applicable US
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Not Available
- CAS number
- 7664-41-7
- InChI Key
- Not Available
- InChI
- Not Available
- IUPAC Name
- Not Available
- SMILES
- Not Available
References
- General References
- KESEL RG, O'DONNELL JF, et al.: The biological production and therapeutic use of ammonia in the oral cavity in relation to dental caries prevention. J Am Dent Assoc. 1946 Jun;33:695-714. [Article]
- Felipo V, Butterworth RF: Neurobiology of ammonia. Prog Neurobiol. 2002 Jul;67(4):259-79. [Article]
- Hakvoort TB, He Y, Kulik W, Vermeulen JL, Duijst S, Ruijter JM, Runge JH, Deutz NE, Koehler SE, Lamers WH: Pivotal role of glutamine synthetase in ammonia detoxification. Hepatology. 2017 Jan;65(1):281-293. doi: 10.1002/hep.28852. Epub 2016 Nov 12. [Article]
- Weiner ID, Verlander JW: Ammonia Transporters and Their Role in Acid-Base Balance. Physiol Rev. 2017 Apr;97(2):465-494. doi: 10.1152/physrev.00011.2016. [Article]
- Ammonia - National Library of Medicine HSDB Database - Toxnet - NIH [Link]
- External Links
- FDA label
- Download (264 KB)
- MSDS
- Download (242 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Autonomic Failure / Multiple System Atrophy (MSA) / Parkinson's Disease (PD) 1 somestatus stop reason just information to hide Not Available Completed Not Available Coronary Artery Disease (CAD) 1 somestatus stop reason just information to hide Not Available Completed Not Available Disorders of the Autonomic Nervous System / Parkinson's Disease (PD) / Progressive autonomic failure 1 somestatus stop reason just information to hide Not Available Completed Diagnostic Coronary Artery Disease (CAD) 1 somestatus stop reason just information to hide 4 Recruiting Diagnostic N-13 Ammonia Safety 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Kit Topical 0.045 g/0.3mL Inhalant; kit; liquid; ointment; spray; tablet Ophthalmic; Oral; Respiratory (inhalation); Topical Gel; inhalant; kit; liquid; ointment Ophthalmic; Respiratory (inhalation); Topical Kit Ophthalmic; Oral; Respiratory (inhalation); Topical Kit Respiratory (inhalation); Topical Kit Ophthalmic; Respiratory (inhalation); Topical Inhalant; kit; liquid; spray; tablet Ophthalmic; Oral; Respiratory (inhalation); Topical Gel; inhalant; kit; liquid; ointment; swab Ophthalmic; Respiratory (inhalation); Topical Cream; inhalant; kit; swab; tablet Oral; Respiratory (inhalation); Topical Kit Oral; Respiratory (inhalation); Topical Inhalant; kit; liquid; ointment; spray; swab Ophthalmic; Respiratory (inhalation); Topical Cream; inhalant; kit; liquid Ophthalmic; Respiratory (inhalation); Topical Inhalant; kit; swab Respiratory (inhalation); Topical Inhalant; kit; liquid; ointment; spray; swab; tablet Ophthalmic; Oral; Respiratory (inhalation); Topical Kit Irrigation; Ophthalmic; Respiratory (inhalation); Topical Kit Irrigation; Oral; Respiratory (inhalation); Topical Kit Irrigation; Ophthalmic; Oral; Respiratory (inhalation); Topical Liquid Topical 3.61 % Liquid Topical 3.5 g/100g Aerosol Respiratory (inhalation) 0.15 g/1g Aerosol Respiratory (inhalation) 0.045 g/0.3mL Swab Respiratory (inhalation) 15 % Inhalant Respiratory (inhalation) 0.045 g/0.3mL Inhalant Respiratory (inhalation) 0.05 g/0.33mL Inhalant Respiratory (inhalation) 0.15 g/1g Liquid Respiratory (inhalation) Inhalant Respiratory (inhalation) 10 mL/100mL Liquid Topical 7 mg/1mL Kit Topical Kit Topical 30 mg/1mL Kit Oral Liquid Nasal; Respiratory (inhalation) Inhalant Respiratory (inhalation) 0.013 mL/0.3mL Kit Infiltration; Intra-articular; Intramuscular; Respiratory (inhalation); Topical Inhalant; injection, solution; injection, suspension; kit; solution Epidural; Infiltration; Intra-articular; Intracaudal; Intramuscular; Perineural; Respiratory (inhalation); Topical Liniment Topical Liquid Topical Lotion Topical 1.5 g/100mL Kit Epidural; Infiltration; Intra-articular; Intracaudal; Intramuscular; Perineural; Respiratory (inhalation); Topical Liquid Topical 20 mg/1mL Solution Cutaneous Syrup Solution Nasal 2.5 mg/100mL Solution Nasal 2.5 g/100mL Elixir Nasal 2.5 g/100mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Gas
- Experimental Properties
Property Value Source melting point (°C) -77.7 MSDS boiling point (°C) -33.4 MSDS - Predicted Properties
- Not Available
- Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketoglutarate. Increases cellular anti-oxidant function via NADH and glutathione production. May play a role in preventing tumor proliferation
- Specific Function
- glutaminase activity
- Gene Name
- GLS2
- Uniprot ID
- Q9UI32
- Uniprot Name
- Glutaminase liver isoform, mitochondrial
- Molecular Weight
- 66322.225 Da
References
- Ammonia - National Library of Medicine HSDB Database - Toxnet - NIH [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine (PubMed:16267323, PubMed:30158707, PubMed:36289327). Its role depends on tissue localization: in the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, it is one of the enzymes responsible for the removal of ammonia (By similarity). Essential for proliferation of fetal skin fibroblasts (PubMed:18662667). Independently of its glutamine synthetase activity, required for endothelial cell migration during vascular development: acts by regulating membrane localization and activation of the GTPase RHOJ, possibly by promoting RHOJ palmitoylation (PubMed:30158707). May act as a palmitoyltransferase for RHOJ: able to autopalmitoylate and then transfer the palmitoyl group to RHOJ (PubMed:30158707). Plays a role in ribosomal 40S subunit biogenesis (PubMed:26711351). Through the interaction with BEST2, inhibits BEST2 channel activity by affecting the gating at the aperture in the absence of intracellular L-glutamate, but sensitizes BEST2 to intracellular L-glutamate, which promotes the opening of BEST2 and thus relieves its inhibitory effect on BEST2 (PubMed:36289327)
- Specific Function
- ATP binding
- Gene Name
- GLUL
- Uniprot ID
- P15104
- Uniprot Name
- Glutamine synthetase
- Molecular Weight
- 42064.15 Da
References
- Ammonia - National Library of Medicine HSDB Database - Toxnet - NIH [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell
- Specific Function
- ATP binding
- Gene Name
- CPS1
- Uniprot ID
- P31327
- Uniprot Name
- Carbamoyl-phosphate synthase [ammonia], mitochondrial
- Molecular Weight
- 164938.145 Da
References
- Ammonia - National Library of Medicine HSDB Database - Toxnet - NIH [Link]
Drug created at December 03, 2015 16:51 / Updated at June 12, 2020 16:53