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Details

Stereochemistry ACHIRAL
Molecular Formula C21H29N2O.Cl
Molecular Weight 360.9215
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DENATONIUM CHLORIDE

SMILES

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

InChI

InChIKey=YNQALPDYZRNHNK-UHFFFAOYSA-N
InChI=1S/C21H28N2O.ClH/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;1H

HIDE SMILES / InChI

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 ClH
Molecular Weight 36.4609
Charge 0
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
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
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
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
Taste + odor interactions in compound aversion conditioning.
2004 Nov
Genomic organization, expression, and function of bitter taste receptors (T2R) in mouse and rat.
2005 Jul 14
Inbred mouse strains C57BL/6J and DBA/2J vary in sensitivity to a subset of bitter stimuli.
2005 Jun 20
Haplotypes at the Tas2r locus on distal chromosome 6 vary with quinine taste sensitivity in inbred mice.
2005 Jun 6
G-protein signaling: back to the future.
2005 Mar
Characterization of bitter taste responses of intestinal STC-1 cells.
2005 May
Bitterness suppression with zinc sulfate and na-cyclamate: a model of combined peripheral and central neural approaches to flavor modification.
2005 Nov
G-protein-dependent and -independent pathways in denatonium signal transduction.
2005 Sep
PLCbeta2-independent behavioral avoidance of prototypical bitter-tasting ligands.
2005 Sep
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
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
A non-invasive method for ending thumb- and fingersucking habits.
2007 Oct
Construction of a taste-blind medaka fish and quantitative assay of its preference-aversion behavior.
2008 Nov
Constructing quality profiles for taste compounds in rats: a novel paradigm.
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
Signalling mechanisms in mouse bitter responsive taste cells.
2009 Jul 1
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 Fri Jun 25 23:22:29 UTC 2021
Edited
by admin
on Fri Jun 25 23:22:29 UTC 2021
Record UNII
0W5171805N
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DENATONIUM CHLORIDE
VANDF  
Common Name English
DENATONIUM CHLORIDE [VANDF]
Common Name English
BENZENEMETHANAMINIUM, N-(2-((2,6-DIMETHYLPHENYL)AMINO)-2-OXOETHYL)-N,N-DIETHYL-, CHLORIDE (1:1)
Systematic Name English
BENZENEMETHANAMINIUM, N-(2-((2,6-DIMETHYLPHENYL)AMINO)-2-OXOETHYL)-N,N-DIETHYL-, CHLORIDE
Systematic Name English
Code System Code Type Description
FDA UNII
0W5171805N
Created by admin on Fri Jun 25 23:22:29 UTC 2021 , Edited by admin on Fri Jun 25 23:22:29 UTC 2021
PRIMARY
MESH
C043414
Created by admin on Fri Jun 25 23:22:29 UTC 2021 , Edited by admin on Fri Jun 25 23:22:29 UTC 2021
PRIMARY
PUBCHEM
15487
Created by admin on Fri Jun 25 23:22:29 UTC 2021 , Edited by admin on Fri Jun 25 23:22:29 UTC 2021
PRIMARY
CAS
1674-99-3
Created by admin on Fri Jun 25 23:22:29 UTC 2021 , Edited by admin on Fri Jun 25 23:22:29 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY