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Details

Stereochemistry ACHIRAL
Molecular Formula C21H29N2O
Molecular Weight 325.4678
Optical Activity NONE
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 1

SHOW SMILES / InChI
Structure of DENATONIUM

SMILES

CC[N+](CC)(CC(=O)NC1=C(C)C=CC=C1C)CC2=CC=CC=C2

InChI

InChIKey=ZFQMTVNLDNXRNQ-UHFFFAOYSA-O
InChI=1S/C21H28N2O/c1-5-23(6-2,15-19-13-8-7-9-14-19)16-20(24)22-21-17(3)11-10-12-18(21)4/h7-14H,5-6,15-16H2,1-4H3/p+1

HIDE SMILES / InChI

Molecular Formula C21H29N2O
Molecular Weight 325.4678
Charge 1
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity NONE

Denatonium, usually available as denatonium benzoate (trade names Bitrex) is the most bitter chemical compound known, with bitterness thresholds of 0.05 ppm for the benzoate and 0.01 ppm for the saccharide. Scientists at Macfarlan Smith, Ltd. of Edinburgh, Scotland discovered Bitrex during research on derivatives of the anesthetic lidocaine. The extremely bitter taste proved effective in reducing ingestion by humans and animals. Denatonium is commonly included in placebo medications used in clinical trials to match the bitter taste of certain medications. Denatonium activates bitter taste receptor, mainly, TAS2R4, TAS2R8, TAS2R10, TAS2R13 on many cell types and plays important roles in chemical release, ciliary beating and smooth muscle relaxation through intracellular Ca(2+)-dependent pathways.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q9NYW5
Gene ID: 50832.0
Gene Symbol: TAS2R4
Target Organism: Homo sapiens (Human)
Target ID: Q9NYV9
Gene ID: 50838.0
Gene Symbol: TAS2R13
Target Organism: Homo sapiens (Human)
Target ID: Q9NYW0
Gene ID: 50839.0
Gene Symbol: TAS2R10
Target Organism: Homo sapiens (Human)
Target ID: Q9NYW2
Gene ID: 50836.0
Gene Symbol: TAS2R8
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Doses

Doses

DosePopulationAdverse events​
300 ppm single, ophthalmic
Dose: 300 ppm
Route: ophthalmic
Route: single
Dose: 300 ppm
Sources:
healthy, 27 years (range: 22–33 years)
Health Status: healthy
Age Group: 27 years (range: 22–33 years)
Sex: M+F
Sources:
1 umol/kg single, intragastric
Dose: 1 umol/kg
Route: intragastric
Route: single
Dose: 1 umol/kg
Sources:
healthy, 29 years
Health Status: healthy
Age Group: 29 years
Sex: M+F
Sources:
1.69 mg/mL single, respiratory
Dose: 1.69 mg/mL
Route: respiratory
Route: single
Dose: 1.69 mg/mL
Sources:
healthy, 34 years
Health Status: healthy
Age Group: 34 years
Sex: F
Sources:
Other AEs: Asthma...
Other AEs:
Asthma (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Asthma 1 patient
1.69 mg/mL single, respiratory
Dose: 1.69 mg/mL
Route: respiratory
Route: single
Dose: 1.69 mg/mL
Sources:
healthy, 34 years
Health Status: healthy
Age Group: 34 years
Sex: F
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction.
2001
Bitter taste transduced by PLC-beta(2)-dependent rise in IP(3) and alpha-gustducin-dependent fall in cyclic nucleotides.
2001 Apr
Soa genotype selectively affects mouse gustatory neural responses to sucrose octaacetate.
2001 Apr 27
Taste receptor cells that discriminate between bitter stimuli.
2001 Feb 23
Cellular responses of NG108-15 and SK-N-MC lines to sweet and bitter tastants as measured by extracellular acidification rates.
2001 Jan 1
Covariation in individuals' sensitivities to bitter compounds: evidence supporting multiple receptor/transduction mechanisms.
2001 Jul
Effect of compound sequence on bitterness enhancement.
2001 May
Taste receptor cell responses to the bitter stimulus denatonium involve Ca2+ influx via store-operated channels.
2002 Jun
Rats fail to discriminate quinine from denatonium: implications for the neural coding of bitter-tasting compounds.
2002 Mar 1
Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli.
2003 Oct 29
Was it necessary to add Bitrex (denatonium benzoate) to automotive products?
2004 Jun
Taste + odor interactions in compound aversion conditioning.
2004 Nov
Identification of ligands for two human bitter T2R receptors.
2004 Sep
Diverse bitter stimuli elicit highly similar patterns of Fos-like immunoreactivity in the nucleus of the solitary tract.
2004 Sep
Umami taste responses are mediated by alpha-transducin and alpha-gustducin.
2004 Sep 1
In vivo imaging of C. elegans ASH neurons: cellular response and adaptation to chemical repellents.
2005 Jan 12
Genomic organization, expression, and function of bitter taste receptors (T2R) in mouse and rat.
2005 Jul 14
Haplotypes at the Tas2r locus on distal chromosome 6 vary with quinine taste sensitivity in inbred mice.
2005 Jun 6
Differential covariation in taste responsiveness to bitter stimuli in rats.
2005 Nov
G-protein-dependent and -independent pathways in denatonium signal transduction.
2005 Sep
Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels.
2006 Oct
Exploratory behaviour in NO-dependent cyclase mutants of Drosophila shows defects in coincident neuronal signalling.
2007 Aug 6
Functional characterization of human bitter taste receptors.
2007 May 1
A non-invasive method for ending thumb- and fingersucking habits.
2007 Oct
The neural processing of taste.
2007 Sep 18
Behavioral genetics and taste.
2007 Sep 18
Adverse reactions associated with respirator fit testing of healthcare workers in British Columbia, Canada: a review of compensation claim cases.
2007 Winter
Final report of the safety assessment of Alcohol Denat., including SD Alcohol 3-A, SD Alcohol 30, SD Alcohol 39, SD Alcohol 39-B, SD Alcohol 39-C, SD Alcohol 40, SD Alcohol 40-B, and SD Alcohol 40-C, and the denaturants, Quassin, Brucine Sulfate/Brucine, and Denatonium Benzoate.
2008
Norepinephrine is coreleased with serotonin in mouse taste buds.
2008 Dec 3
Role of CCK1 and Y2 receptors in activation of hindbrain neurons induced by intragastric administration of bitter taste receptor ligands.
2008 Jan
Responses of the ciliates tetrahymena and paramecium to vertebrate odorants and tastants.
2008 Jan-Feb
The impact of bittering agents on suicidal ingestions of antifreeze.
2008 Jul
Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro.
2008 Jun
Intragastric infusion of denatonium conditions flavor aversions and delays gastric emptying in rodents.
2008 Mar 18
The taste transduction channel TRPM5 is a locus for bitter-sweet taste interactions.
2008 May
Construction of a taste-blind medaka fish and quantitative assay of its preference-aversion behavior.
2008 Nov
Tonic activity of Galpha-gustducin regulates taste cell responsivity.
2008 Nov 12
Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity.
2008 Nov 13
Constructing quality profiles for taste compounds in rats: a novel paradigm.
2008 Oct 20
Preferences of 14 rat strains for 17 taste compounds.
2008 Oct 20
Central Fos expression and conditioned flavor avoidance in rats following intragastric administration of bitter taste receptor ligands.
2009 Mar
A Drosophila gustatory receptor essential for aversive taste and inhibiting male-to-male courtship.
2009 Oct 13
Chemoreception regulates chemical access to mouse vomeronasal organ: role of solitary chemosensory cells.
2010 Jul 30
Vasoactive intestinal peptide-null mice demonstrate enhanced sweet taste preference, dysglycemia, and reduced taste bud leptin receptor expression.
2010 May
Patents

Patents

Sample Use Guides

1 µmol/kg bodyweight (10mM) was administered as a bolus into the stomach through a nasogastric feeding tube.
Route of Administration: Other
Denatonium inhibits growth and induces apoptosis of airway epithelial cells. After treatment with 2 mM denatonium for 24 h, the expression of the anti-apoptotic protein Bcl-2 was significantly reduced and the release of cytochrome c and Smac/DIABLO from the mitochondria to the cytoplasm was drastically increased in human bronchial epithelial cell lines 16HBE. To examine whether denatonium induces mitochondrial damage in airway epithelial cells, was used transmission electron microscopy to examine the ultrastructures of human lung cancer cell line A549 treated with 2 mM denatonium. The control cells appeared to have normal mitochondria and mostly homogeneous cytoplasms, while A549 cells treated with denatonium showed large amplitude swelling of mitochondria.
Substance Class Chemical
Created
by admin
on Mon Mar 31 17:58:54 GMT 2025
Edited
by admin
on Mon Mar 31 17:58:54 GMT 2025
Record UNII
4IK22DF4OU
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BENZENEMETHANAMINIUM, N-(2-((2,6-DIMETHYLPHENYL)AMINO)-2-OXOETHYL)-N,N-DIETHYL
Preferred Name English
DENATONIUM
VANDF   WHO-DD  
Common Name English
BENZYLDIETHYL((2,6-XYLYLCARBAMOYL)METHYL)AMMONIUM
Systematic Name English
DENATONIUM [VANDF]
Common Name English
Denatonium [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C83486
Created by admin on Mon Mar 31 17:58:54 GMT 2025 , Edited by admin on Mon Mar 31 17:58:54 GMT 2025
Code System Code Type Description
WIKIPEDIA
DENATONIUM
Created by admin on Mon Mar 31 17:58:54 GMT 2025 , Edited by admin on Mon Mar 31 17:58:54 GMT 2025
PRIMARY
SMS_ID
100000087748
Created by admin on Mon Mar 31 17:58:54 GMT 2025 , Edited by admin on Mon Mar 31 17:58:54 GMT 2025
PRIMARY
EPA CompTox
DTXSID9043770
Created by admin on Mon Mar 31 17:58:54 GMT 2025 , Edited by admin on Mon Mar 31 17:58:54 GMT 2025
PRIMARY
EVMPD
SUB01582MIG
Created by admin on Mon Mar 31 17:58:54 GMT 2025 , Edited by admin on Mon Mar 31 17:58:54 GMT 2025
PRIMARY
PUBCHEM
15488
Created by admin on Mon Mar 31 17:58:54 GMT 2025 , Edited by admin on Mon Mar 31 17:58:54 GMT 2025
PRIMARY
RXCUI
1546417
Created by admin on Mon Mar 31 17:58:54 GMT 2025 , Edited by admin on Mon Mar 31 17:58:54 GMT 2025
PRIMARY RxNorm
CAS
47324-98-1
Created by admin on Mon Mar 31 17:58:54 GMT 2025 , Edited by admin on Mon Mar 31 17:58:54 GMT 2025
PRIMARY
DAILYMED
4IK22DF4OU
Created by admin on Mon Mar 31 17:58:54 GMT 2025 , Edited by admin on Mon Mar 31 17:58:54 GMT 2025
PRIMARY
NCI_THESAURUS
C83659
Created by admin on Mon Mar 31 17:58:54 GMT 2025 , Edited by admin on Mon Mar 31 17:58:54 GMT 2025
PRIMARY
FDA UNII
4IK22DF4OU
Created by admin on Mon Mar 31 17:58:54 GMT 2025 , Edited by admin on Mon Mar 31 17:58:54 GMT 2025
PRIMARY
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ACTIVE MOIETY