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

Details

Stereochemistry ACHIRAL
Molecular Formula C21H29N2O.C2H3O2
Molecular Weight 384.5127
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DENATONIUM ACETATE

SMILES

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

InChI

InChIKey=MRXPBBXBHPUCQZ-UHFFFAOYSA-N
InChI=1S/C21H28N2O.C2H4O2/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;1-2(3)4/h7-14H,5-6,15-16H2,1-4H3;1H3,(H,3,4)

HIDE SMILES / InChI

Molecular Formula C2H3O2
Molecular Weight 59.0441
Charge -1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C21H29N2O
Molecular Weight 325.4685
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
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)
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
Soa genotype selectively affects mouse gustatory neural responses to sucrose octaacetate.
2001 Apr 27
Bitter substances suppress afferent responses to an appetitive mixture: evidence for peripheral integration of chemosensory stimuli.
2001 Dec
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
Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli.
2003 Oct 29
Saccharin stimulates the "deterrent" cell in the blowfly: behavioral and electrophysiological evidence.
2004 Feb
The distinctiveness of ionic and nonionic bitter stimuli.
2004 Jan
Was it necessary to add Bitrex (denatonium benzoate) to automotive products?
2004 Jun
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
Umami taste responses are mediated by alpha-transducin and alpha-gustducin.
2004 Sep 1
G-protein signaling: back to the future.
2005 Mar
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
Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium.
2007 Jul 25
Functional characterization of human bitter taste receptors.
2007 May 1
Characterization of ligands for fish taste receptors.
2007 May 23
A non-invasive method for ending thumb- and fingersucking habits.
2007 Oct
Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse.
2007 Sep 27
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
Riboflavin-binding protein is a novel bitter inhibitor.
2008 Jan
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
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
Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.
2009
Chemical analysis and risk assessment of diethyl phthalate in alcoholic beverages with special regard to unrecorded alcohol.
2009 Dec 2
Gustatory responsiveness to six bitter tastants in three species of nonhuman primates.
2009 May
Residual chemosensory capabilities in double P2X2/P2X3 purinergic receptor null mice: intraoral or postingestive detection?
2009 Nov
A Drosophila gustatory receptor essential for aversive taste and inhibiting male-to-male courtship.
2009 Oct 13
Discrimination of taste qualities among mouse fungiform taste bud cells.
2009 Sep 15
Molecular and cellular designs of insect taste receptor system.
2010
Chemoreception regulates chemical access to mouse vomeronasal organ: role of solitary chemosensory cells.
2010 Jul 30
Responses of single chorda tympani taste fibers of the calf (Bos taurus).
2010 Jun
Vasoactive intestinal peptide-null mice demonstrate enhanced sweet taste preference, dysglycemia, and reduced taste bud leptin receptor expression.
2010 May
Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction.
2010 Nov
Ghrelin is produced in taste cells and ghrelin receptor null mice show reduced taste responsivity to salty (NaCl) and sour (citric acid) tastants.
2010 Sep 14
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 Sat Jun 26 07:54:56 UTC 2021
Edited
by admin
on Sat Jun 26 07:54:56 UTC 2021
Record UNII
8QG4DAT7RW
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DENATONIUM ACETATE
Common Name English
BENZENEMETHANAMINIUM, N-(2-((2,6-DIMETHYLPHENYL)AMINO)-2-OXOETHYL)-N,N-DIETHYL-, ACETATE (1:1)
Common Name English
Code System Code Type Description
PUBCHEM
118353494
Created by admin on Sat Jun 26 07:54:56 UTC 2021 , Edited by admin on Sat Jun 26 07:54:56 UTC 2021
PRIMARY
FDA UNII
8QG4DAT7RW
Created by admin on Sat Jun 26 07:54:56 UTC 2021 , Edited by admin on Sat Jun 26 07:54:56 UTC 2021
PRIMARY
CAS
1995890-04-4
Created by admin on Sat Jun 26 07:54:56 UTC 2021 , Edited by admin on Sat Jun 26 07:54:56 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY