DENATONIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H29N2O
Molecular Weight	325.4678
Optical Activity	NONE
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	1

SHOW SMILES / InChI

Structure Search

SMILES

CC[N+](CC)(CC(=O)NC1=C(C)C=CC=C1C)CC2=CC=CC=C2

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

Molecular Formula	C21H29N2O
Molecular Weight	325.4678
Charge	1
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.marketactives.com/bitrex-bittering-agent/ | https://www.ncbi.nlm.nih.gov/pubmed/20022913

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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Taste receptor type 2 member 4 7 Target ID: Q9NYW5 Gene ID: 50832.0 Gene Symbol: TAS2R4 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20022913	Agonist 2752
Taste receptor type 2 member 13 7 Target ID: Q9NYV9 Gene ID: 50838.0 Gene Symbol: TAS2R13 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20022913	Agonist 2752
Taste receptor type 2 member 10 7 Target ID: Q9NYW0 Gene ID: 50839.0 Gene Symbol: TAS2R10 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20022913	Agonist 2752
Taste receptor type 2 member 8 7 Target ID: Q9NYW2 Gene ID: 50836.0 Gene Symbol: TAS2R8 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20022913	Agonist 2752

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2596

Doses

Dose	Population	Adverse events
300 ppm single, ophthalmic Dose: 300 ppm Route: ophthalmic Route: single Dose: 300 ppm Sources: https://pubmed.ncbi.nlm.nih.gov/30502985	healthy, 27 years (range: 22–33 years) Health Status: healthy Age Group: 27 years (range: 22–33 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/30502985	Sources: https://pubmed.ncbi.nlm.nih.gov/30502985
1 umol/kg single, intragastric Dose: 1 umol/kg Route: intragastric Route: single Dose: 1 umol/kg Sources: https://pubmed.ncbi.nlm.nih.gov/28148502/	healthy, 29 years Health Status: healthy Age Group: 29 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28148502/	Sources: https://pubmed.ncbi.nlm.nih.gov/28148502/
1.69 mg/mL single, respiratory Dose: 1.69 mg/mL Route: respiratory Route: single Dose: 1.69 mg/mL Sources: https://pubmed.ncbi.nlm.nih.gov/31124982	healthy, 34 years Health Status: healthy Age Group: 34 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/31124982	Other AEs: Asthma... Other AEs: Asthma (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/31124982

AEs

AE	Significance	Dose	Population
Asthma	1 patient	1.69 mg/mL single, respiratory Dose: 1.69 mg/mL Route: respiratory Route: single Dose: 1.69 mg/mL Sources: https://pubmed.ncbi.nlm.nih.gov/31124982	healthy, 34 years Health Status: healthy Age Group: 34 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/31124982

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P006MIS
1PlusChem LLC	1P00I7TG
A2B Chem	AD08324
A2B Chem	AI49140
AA Blocks	AA006LZC
AA Blocks	AA00I7A0
ABI Chem	AC1L25ZU
ABI Chem	AC1Q5LWS
AbovChem LLC	HY-B1146
AK Scientific	O701
AK Scientific	P665
Alfa Chemistry	122908-44-5
Alfa Chemistry	222608-06-2
Ambeed	A181673
Ambeed	A618227
AstaTech	F16467
AstaTech	F20409
Bide Pharmatech	BD123753
BioSynth	W-106547
BLD Pharm	BD123753
BLD Pharm	BD123754
BlocksMatrix Scientific	89226
BlocksMatrix Scientific	98530
BOC Sciences	122908-44-5
BOC Sciences	1674-99-3
BOC Sciences	222608-06-2
BOC Sciences	3734-33-6
BOC Sciences	90823-38-4
Bosche Scientific	D2863
Chem-Impex International	24137
Chem Scene	CS-4750
Combi-Blocks	QA-6116
Combi-Blocks	SS-9638
Compound Cloud	15488
Compound Cloud	168900
eMolecules	109860763
eMolecules	313070398
eMolecules	33664792
eMolecules	496852
eMolecules	6886257
eNovation Chemicals	D584553
eNovation Chemicals	D769907
Hairui	HR103476
Hairui	HR138147
Hairui	HR138408
Hangzhou APIChem Technology	AC-14888
Hangzhou Yuhao Chemical Technology	HL2593
Hangzhou Yuhao Chemical Technology	HL4177
Hangzhou Yuhao Chemical Technology	LQ1874
Heteroz	10286
HongKong Chemhere	90823-38-4
KeyOrganics	AS-15271
KeyOrganics	AS-15511
Lab Network	LN00196762	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00196762
Lab Seeker	SC-13384
Lab Seeker	SC-17476
mcule	MCULE-9057328681	https://mcule.com/MCULE-9057328681/
MedChem Express	HY-B1146
Molnova	M14290
MolPort	MolPort-003-929-793
MolPort	MolPort-009-679-949
MuseChem	M011722
MuseChem	M028211
MuseChem	M119750
MuseChem	R023805
Norris Pharm	NSZB-A221975
Norris Pharm	NSZB-A221976
Oakwood	95403
PI Chemicals	PI-20337
PI Chemicals	PI-20338
Ryan Scientific	Perphenazine
Scientific Exchange	POD_05/0837
Scientific Exchange	POD_09/0054
Sigma Aldrich	1171003
Sigma Aldrich	52487
Sigma Aldrich	52487\|SIAL
Sigma Aldrich	93675\|SIAL
Sigma Aldrich	D5765\|ALDRICH
StruChem	SC-13384
StruChem	SC-17476
TargetMol	T1098
Tetrahedron	TS82315
Tetrahedron	TS83323
TimTec	SBB057812
TimTec	ST51007042
Toronto Research Chemicals	C724810
Toronto Research Chemicals	D231660
Toronto Research Chemicals	D231705
Vesino Industrial Co Ltd	VA10687
W&J PharmaChem	50C151785
ZINC	ZINC000001601437	http://zinc15.docking.org/substances/ZINC000001601437

PubMed

Title	Date	PubMed
Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction.	2001	11346454
Bitter taste transduced by PLC-beta(2)-dependent rise in IP(3) and alpha-gustducin-dependent fall in cyclic nucleotides.	2001 Apr	11245589
Soa genotype selectively affects mouse gustatory neural responses to sucrose octaacetate.	2001 Apr 27	11328963
Taste receptor cells that discriminate between bitter stimuli.	2001 Feb 23	11222863
Cellular responses of NG108-15 and SK-N-MC lines to sweet and bitter tastants as measured by extracellular acidification rates.	2001 Jan 1	11169615
Covariation in individuals' sensitivities to bitter compounds: evidence supporting multiple receptor/transduction mechanisms.	2001 Jul	11521845
Effect of compound sequence on bitterness enhancement.	2001 May	11369676
Taste receptor cell responses to the bitter stimulus denatonium involve Ca2+ influx via store-operated channels.	2002 Jun	12037215
Rats fail to discriminate quinine from denatonium: implications for the neural coding of bitter-tasting compounds.	2002 Mar 1	11880524
Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli.	2003 Oct 29	14586025
Was it necessary to add Bitrex (denatonium benzoate) to automotive products?	2004 Jun	15171494
Taste + odor interactions in compound aversion conditioning.	2004 Nov	15825885
Identification of ligands for two human bitter T2R receptors.	2004 Sep	15337684
Diverse bitter stimuli elicit highly similar patterns of Fos-like immunoreactivity in the nucleus of the solitary tract.	2004 Sep	15337683
Umami taste responses are mediated by alpha-transducin and alpha-gustducin.	2004 Sep 1	15342734
In vivo imaging of C. elegans ASH neurons: cellular response and adaptation to chemical repellents.	2005 Jan 12	15577941
Genomic organization, expression, and function of bitter taste receptors (T2R) in mouse and rat.	2005 Jul 14	15886333
Haplotypes at the Tas2r locus on distal chromosome 6 vary with quinine taste sensitivity in inbred mice.	2005 Jun 6	15938754
Differential covariation in taste responsiveness to bitter stimuli in rats.	2005 Nov	16267162
G-protein-dependent and -independent pathways in denatonium signal transduction.	2005 Sep	16195580
Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels.	2006 Oct	16707556
Exploratory behaviour in NO-dependent cyclase mutants of Drosophila shows defects in coincident neuronal signalling.	2007 Aug 6	17683617
Functional characterization of human bitter taste receptors.	2007 May 1	17253962
A non-invasive method for ending thumb- and fingersucking habits.	2007 Oct	18175885
The neural processing of taste.	2007 Sep 18	17903281
Behavioral genetics and taste.	2007 Sep 18	17903279
Adverse reactions associated with respirator fit testing of healthcare workers in British Columbia, Canada: a review of compensation claim cases.	2007 Winter	18458024
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	18569160
Norepinephrine is coreleased with serotonin in mouse taste buds.	2008 Dec 3	19052199
Role of CCK1 and Y2 receptors in activation of hindbrain neurons induced by intragastric administration of bitter taste receptor ligands.	2008 Jan	18003792
Responses of the ciliates tetrahymena and paramecium to vertebrate odorants and tastants.	2008 Jan-Feb	18251800
The impact of bittering agents on suicidal ingestions of antifreeze.	2008 Jul	18584362
Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro.	2008 Jun	18417634
Intragastric infusion of denatonium conditions flavor aversions and delays gastric emptying in rodents.	2008 Mar 18	18174110
The taste transduction channel TRPM5 is a locus for bitter-sweet taste interactions.	2008 May	18070821
Construction of a taste-blind medaka fish and quantitative assay of its preference-aversion behavior.	2008 Nov	18700838
Tonic activity of Galpha-gustducin regulates taste cell responsivity.	2008 Nov 12	18930056
Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity.	2008 Nov 13	19014531
Constructing quality profiles for taste compounds in rats: a novel paradigm.	2008 Oct 20	18664369
Preferences of 14 rat strains for 17 taste compounds.	2008 Oct 20	18639567
Central Fos expression and conditioned flavor avoidance in rats following intragastric administration of bitter taste receptor ligands.	2009 Mar	19073908
A Drosophila gustatory receptor essential for aversive taste and inhibiting male-to-male courtship.	2009 Oct 13	19765987
Chemoreception regulates chemical access to mouse vomeronasal organ: role of solitary chemosensory cells.	2010 Jul 30	20689832
Vasoactive intestinal peptide-null mice demonstrate enhanced sweet taste preference, dysglycemia, and reduced taste bud leptin receptor expression.	2010 May	20150284

Patents

Sample Use Guides

In Vivo Use Guide

1 µmol/kg bodyweight (10mM) was administered as a bolus into the stomach through a nasogastric feeding tube.

Route of Administration: Other

In Vitro Use Guide

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 `Mon Mar 31 17:58:54 GMT 2025` Edited by `admin` on `Mon Mar 31 17:58:54 GMT 2025`
Record UNII	4IK22DF4OU
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BENZENEMETHANAMINIUM, N-(2-((2,6-DIMETHYLPHENYL)AMINO)-2-OXOETHYL)-N,N-DIETHYL

Preferred Name

English

DENATONIUM

Common Name

English

BENZYLDIETHYL((2,6-XYLYLCARBAMOYL)METHYL)AMMONIUM

Systematic Name

English

DENATONIUM [VANDF]

Common Name

English

Denatonium [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C83486