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Details

Stereochemistry ACHIRAL
Molecular Formula C21H29N2O.C7H5O2.H2O
Molecular Weight 464.5975
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DENATONIUM BENZOATE

SMILES

CC[N+](CC)(Cc1ccccc1)CC(=Nc2c(C)cccc2C)[O-].c1ccc(cc1)C(=O)O.O

InChI

InChIKey=YYMVPVZYUYQSJE-UHFFFAOYSA-N
InChI=1S/C21H28N2O.C7H6O2.H2O/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;8-7(9)6-4-2-1-3-5-6;/h7-14H,5-6,15-16H2,1-4H3;1-5H,(H,8,9);1H2

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
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 RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C7H5O2
Molecular Weight 121.1137
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
Chemotaxis of the nematode Caenorhabditis elegans toward cycloheximide and quinine hydrochloride.
2001
Differential covariation in taste responsiveness to bitter stimuli in rats.
2005 Nov
Acute ethanol intoxication after consumption of hairspray.
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
Exploratory behaviour in NO-dependent cyclase mutants of Drosophila shows defects in coincident neuronal signalling.
2007 Aug 6
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
The neural processing of taste.
2007 Sep 18
Behavioral genetics and taste.
2007 Sep 18
Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse.
2007 Sep 27
Predators' toxin burdens influence their strategic decisions to eat toxic prey.
2007 Sep 4
Adverse reactions associated with respirator fit testing of healthcare workers in British Columbia, Canada: a review of compensation claim cases.
2007 Winter
Bitter taste receptors influence glucose homeostasis.
2008
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
Riboflavin-binding protein is a novel bitter inhibitor.
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
Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.
2009
Gustation in fish: search for prototype of taste perception.
2009
Chemical analysis and risk assessment of diethyl phthalate in alcoholic beverages with special regard to unrecorded alcohol.
2009 Dec 2
Delineation of the chemomechanosensory regulation of gastrin secretion using pure rodent G cells.
2009 Jul
Signalling mechanisms in mouse bitter responsive taste cells.
2009 Jul 1
Bitter-responsive gustatory neurons in the rat parabrachial nucleus.
2009 Mar
Central Fos expression and conditioned flavor avoidance in rats following intragastric administration of bitter taste receptor ligands.
2009 Mar
Gustatory responsiveness to six bitter tastants in three species of nonhuman primates.
2009 May
Contribution of the T1r3 taste receptor to the response properties of central gustatory neurons.
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 Fri Jun 25 23:05:42 UTC 2021
Edited
by admin
on Fri Jun 25 23:05:42 UTC 2021
Record UNII
4YK5Z54AT2
Record Status Validated (UNII)
Record Version
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Name Type Language
DENATONIUM BENZOATE
II   MART.   USAN   VANDF  
USAN  
Official Name English
BENZENEMETHANAMINIUM, N-(2-((2,6-DIMETHYLPHENYL)AMINO)-2-OXOETHYL)-N,N-DIETHYL-, BENZOATE, HYDRATE (1:1:1)
Systematic Name English
DENATONIUM BENZOATE [MART.]
Common Name English
BENZYLDIETHYL((2,6-XYLYLCARBAMOYL)METHYL)AMMONIUM BENZOATE MONOHYDRATE
Systematic Name English
DENATONIUM BENZOATE [VANDF]
Common Name English
BITREX
Brand Name English
DENATONIUM BENZOATE [II]
Common Name English
DENATONIUM BENZOATE MONOHYDRATE
Common Name English
LIDOCAINE BENZYL BENZOATE HYDRATE
Common Name English
BENZENEMETHANAMINIUM, N-(2-((2,6-DIMETHYLPHENYL)AMINO)-2-OXOETHYL)-N,N-DIETHYL-, BENZOATE, MONOHYDRATE
Systematic Name English
DENATONIUM BENZOATE HYDRATE
Common Name English
DENATONIUM BENZOATE [USP-RS]
Common Name English
DENATONIUM BENZOATE [USAN]
Common Name English
Classification Tree Code System Code
CFR 21 CFR 310.536
Created by admin on Fri Jun 25 23:05:42 UTC 2021 , Edited by admin on Fri Jun 25 23:05:42 UTC 2021
NCI_THESAURUS C83486
Created by admin on Fri Jun 25 23:05:42 UTC 2021 , Edited by admin on Fri Jun 25 23:05:42 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL1738972
Created by admin on Fri Jun 25 23:05:42 UTC 2021 , Edited by admin on Fri Jun 25 23:05:42 UTC 2021
PRIMARY
MESH
C029408
Created by admin on Fri Jun 25 23:05:42 UTC 2021 , Edited by admin on Fri Jun 25 23:05:42 UTC 2021
PRIMARY
NCI_THESAURUS
C76704
Created by admin on Fri Jun 25 23:05:42 UTC 2021 , Edited by admin on Fri Jun 25 23:05:42 UTC 2021
PRIMARY
USP_CATALOG
1171003
Created by admin on Fri Jun 25 23:05:42 UTC 2021 , Edited by admin on Fri Jun 25 23:05:42 UTC 2021
PRIMARY USP-RS
CAS
86398-53-0
Created by admin on Fri Jun 25 23:05:42 UTC 2021 , Edited by admin on Fri Jun 25 23:05:42 UTC 2021
PRIMARY
EPA CompTox
86398-53-0
Created by admin on Fri Jun 25 23:05:42 UTC 2021 , Edited by admin on Fri Jun 25 23:05:42 UTC 2021
PRIMARY
RXCUI
1313232
Created by admin on Fri Jun 25 23:05:42 UTC 2021 , Edited by admin on Fri Jun 25 23:05:42 UTC 2021
PRIMARY RxNorm
PUBCHEM
168900
Created by admin on Fri Jun 25 23:05:42 UTC 2021 , Edited by admin on Fri Jun 25 23:05:42 UTC 2021
PRIMARY
FDA UNII
4YK5Z54AT2
Created by admin on Fri Jun 25 23:05:42 UTC 2021 , Edited by admin on Fri Jun 25 23:05:42 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY