U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C21H29N2O
Molecular Weight 325.4685
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 1

SHOW SMILES / InChI
Structure of DENATONIUM

SMILES

CC[N+](CC)(Cc1ccccc1)CC(=Nc2c(C)cccc2C)O

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
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)
n = 14
Health Status: healthy
Age Group: 27 years (range: 22–33 years)
Sex: M+F
Population Size: 14
Sources:
1 umol/kg single, intragastric
Dose: 1 umol/kg
Route: intragastric
Route: single
Dose: 1 umol/kg
Sources:
healthy, 29 years
n = 65
Health Status: healthy
Age Group: 29 years
Sex: M+F
Population Size: 65
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
n = 1
Health Status: healthy
Age Group: 34 years
Sex: F
Population Size: 1
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
n = 1
Health Status: healthy
Age Group: 34 years
Sex: F
Population Size: 1
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Bitter substances suppress afferent responses to an appetitive mixture: evidence for peripheral integration of chemosensory stimuli.
2001 Dec
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
Partial rescue of taste responses of alpha-gustducin null mice by transgenic expression of alpha-transducin.
2002 Oct
Stimulation of insulin secretion by denatonium, one of the most bitter-tasting substances known.
2003 Feb
Comparison of the responses of the chorda tympani and glossopharyngeal nerves to taste stimuli in C57BL/6J mice.
2003 Mar 4
A psychophysical investigation of binary bitter-compound interactions.
2003 May
Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli.
2003 Oct 29
Behavioral evidence for a role of alpha-gustducin in glutamate taste.
2003 Sep
The distinctiveness of ionic and nonionic bitter stimuli.
2004 Jan
Taste + odor interactions in compound aversion conditioning.
2004 Nov
Diverse bitter stimuli elicit highly similar patterns of Fos-like immunoreactivity in the nucleus of the solitary tract.
2004 Sep
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
G-protein signaling: back to the future.
2005 Mar
Characterization of bitter taste responses of intestinal STC-1 cells.
2005 May
Differential covariation in taste responsiveness to bitter stimuli in rats.
2005 Nov
Trpm5 null mice respond to bitter, sweet, and umami compounds.
2006 Mar
Mouse taste cells with G protein-coupled taste receptors lack voltage-gated calcium channels and SNAP-25.
2006 Mar 30
Single neurons in the nucleus of the solitary tract respond selectively to bitter taste stimuli.
2006 Nov
Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels.
2006 Oct
Functional characterization of human bitter taste receptors.
2007 May 1
Characterization of ligands for fish taste receptors.
2007 May 23
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
The impact of bittering agents on suicidal ingestions of antifreeze.
2008 Jul
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
Delineation of the chemomechanosensory regulation of gastrin secretion using pure rodent G cells.
2009 Jul
Central Fos expression and conditioned flavor avoidance in rats following intragastric administration of bitter taste receptor ligands.
2009 Mar
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.
Name Type Language
DENATONIUM
VANDF   WHO-DD  
Common Name English
BENZYLDIETHYL((2,6-XYLYLCARBAMOYL)METHYL)AMMONIUM
Systematic Name English
BENZENEMETHANAMINIUM, N-(2-((2,6-DIMETHYLPHENYL)AMINO)-2-OXOETHYL)-N,N-DIETHYL
Common 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 Fri Jun 25 22:53:22 UTC 2021 , Edited by admin on Fri Jun 25 22:53:22 UTC 2021
Code System Code Type Description
WIKIPEDIA
DENATONIUM
Created by admin on Fri Jun 25 22:53:22 UTC 2021 , Edited by admin on Fri Jun 25 22:53:22 UTC 2021
PRIMARY
EPA CompTox
47324-98-1
Created by admin on Fri Jun 25 22:53:22 UTC 2021 , Edited by admin on Fri Jun 25 22:53:22 UTC 2021
PRIMARY
EVMPD
SUB01582MIG
Created by admin on Fri Jun 25 22:53:22 UTC 2021 , Edited by admin on Fri Jun 25 22:53:22 UTC 2021
PRIMARY
PUBCHEM
15488
Created by admin on Fri Jun 25 22:53:22 UTC 2021 , Edited by admin on Fri Jun 25 22:53:22 UTC 2021
PRIMARY
RXCUI
1546417
Created by admin on Fri Jun 25 22:53:22 UTC 2021 , Edited by admin on Fri Jun 25 22:53:22 UTC 2021
PRIMARY RxNorm
CAS
47324-98-1
Created by admin on Fri Jun 25 22:53:22 UTC 2021 , Edited by admin on Fri Jun 25 22:53:22 UTC 2021
PRIMARY
NCI_THESAURUS
C83659
Created by admin on Fri Jun 25 22:53:22 UTC 2021 , Edited by admin on Fri Jun 25 22:53:22 UTC 2021
PRIMARY
FDA UNII
4IK22DF4OU
Created by admin on Fri Jun 25 22:53:22 UTC 2021 , Edited by admin on Fri Jun 25 22:53:22 UTC 2021
PRIMARY