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Details

Stereochemistry ACHIRAL
Molecular Formula C21H29N2O.C7H5O2.H2O
Molecular Weight 464.5964
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DENATONIUM BENZOATE

SMILES

O.[O-]C(=O)C1=CC=CC=C1.CC[N+](CC)(CC(=O)NC2=C(C)C=CC=C2C)CC3=CC=CC=C3

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
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
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
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
Was it necessary to add Bitrex (denatonium benzoate) to automotive products?
2004 Jun
Umami taste responses are mediated by alpha-transducin and alpha-gustducin.
2004 Sep 1
Haplotypes at the Tas2r locus on distal chromosome 6 vary with quinine taste sensitivity in inbred mice.
2005 Jun 6
Acute ethanol intoxication after consumption of hairspray.
2005 Nov
G-protein-dependent and -independent pathways in denatonium signal transduction.
2005 Sep
Mouse taste cells with G protein-coupled taste receptors lack voltage-gated calcium channels and SNAP-25.
2006 Mar 30
Exploratory behaviour in NO-dependent cyclase mutants of Drosophila shows defects in coincident neuronal signalling.
2007 Aug 6
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
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
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
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
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
Delineation of the chemomechanosensory regulation of gastrin secretion using pure rodent G cells.
2009 Jul
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
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
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 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 Wed Jul 05 22:31:26 UTC 2023 , Edited by admin on Wed Jul 05 22:31:26 UTC 2023
NCI_THESAURUS C83486
Created by admin on Wed Jul 05 22:31:26 UTC 2023 , Edited by admin on Wed Jul 05 22:31:26 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL1738972
Created by admin on Wed Jul 05 22:31:26 UTC 2023 , Edited by admin on Wed Jul 05 22:31:26 UTC 2023
PRIMARY
MESH
C029408
Created by admin on Wed Jul 05 22:31:26 UTC 2023 , Edited by admin on Wed Jul 05 22:31:26 UTC 2023
PRIMARY
NCI_THESAURUS
C76704
Created by admin on Wed Jul 05 22:31:26 UTC 2023 , Edited by admin on Wed Jul 05 22:31:26 UTC 2023
PRIMARY
CAS
86398-53-0
Created by admin on Wed Jul 05 22:31:26 UTC 2023 , Edited by admin on Wed Jul 05 22:31:26 UTC 2023
PRIMARY
SMS_ID
100000083715
Created by admin on Wed Jul 05 22:31:26 UTC 2023 , Edited by admin on Wed Jul 05 22:31:26 UTC 2023
PRIMARY
EPA CompTox
DTXSID50235522
Created by admin on Wed Jul 05 22:31:26 UTC 2023 , Edited by admin on Wed Jul 05 22:31:26 UTC 2023
PRIMARY
RXCUI
1313232
Created by admin on Wed Jul 05 22:31:26 UTC 2023 , Edited by admin on Wed Jul 05 22:31:26 UTC 2023
PRIMARY RxNorm
DAILYMED
4YK5Z54AT2
Created by admin on Wed Jul 05 22:31:26 UTC 2023 , Edited by admin on Wed Jul 05 22:31:26 UTC 2023
PRIMARY
PUBCHEM
168900
Created by admin on Wed Jul 05 22:31:26 UTC 2023 , Edited by admin on Wed Jul 05 22:31:26 UTC 2023
PRIMARY
FDA UNII
4YK5Z54AT2
Created by admin on Wed Jul 05 22:31:26 UTC 2023 , Edited by admin on Wed Jul 05 22:31:26 UTC 2023
PRIMARY
RS_ITEM_NUM
1171003
Created by admin on Wed Jul 05 22:31:26 UTC 2023 , Edited by admin on Wed Jul 05 22:31:26 UTC 2023
PRIMARY