DENATONIUM BENZOATE

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 Search

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

Molecular Formula	C7H5O2
Molecular Weight	121.1134
Charge	-1
Count

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

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	325.4678
Charge	1
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
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 2678
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 2678
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 2678
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 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2578

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) n = 14 Health Status: healthy Age Group: 27 years (range: 22–33 years) Sex: M+F Population Size: 14 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 n = 65 Health Status: healthy Age Group: 29 years Sex: M+F Population Size: 65 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 n = 1 Health Status: healthy Age Group: 34 years Sex: F Population Size: 1 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 n = 1 Health Status: healthy Age Group: 34 years Sex: F Population Size: 1 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
AK Scientific	O701
AK Scientific	P665
AbovChem LLC	HY-B1146
Alfa Chemistry	122908-44-5
Alfa Chemistry	222608-06-2
Ambeed	A181673
Ambeed	A618227
AstaTech	F16467
AstaTech	F20409
BLD Pharm	BD123753
BLD Pharm	BD123754
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
Bide Pharmatech	BD123753
BioSynth	W-106547
BlocksMatrix Scientific	89226
BlocksMatrix Scientific	98530
Bosche Scientific	D2863
Chem Scene	CS-4750
Chem-Impex International	24137
Combi-Blocks	QA-6116
Combi-Blocks	SS-9638
Compound Cloud	15488
Compound Cloud	168900
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
MedChem Express	HY-B1146
MolPort	MolPort-003-929-793
MolPort	MolPort-009-679-949
Molnova	M14290
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
eMolecules	109860763
eMolecules	313070398
eMolecules	33664792
eMolecules	496852
eMolecules	6886257
eNovation Chemicals	D584553
eNovation Chemicals	D769907
mcule	MCULE-9057328681	https://mcule.com/MCULE-9057328681/

PubMed

Title	Date	PubMed
Chemotaxis of the nematode Caenorhabditis elegans toward cycloheximide and quinine hydrochloride.	2001	16232999
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
Effect of compound sequence on bitterness enhancement.	2001 May	11369676
Stimulation of insulin secretion by denatonium, one of the most bitter-tasting substances known.	2003 Feb	12540608
Comparison of the responses of the chorda tympani and glossopharyngeal nerves to taste stimuli in C57BL/6J mice.	2003 Mar 4	12617752
A psychophysical investigation of binary bitter-compound interactions.	2003 May	12771017
Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli.	2003 Oct 29	14586025
Behavioral evidence for a role of alpha-gustducin in glutamate taste.	2003 Sep	14578119
Identification of ligands for two human bitter T2R receptors.	2004 Sep	15337684
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
Inbred mouse strains C57BL/6J and DBA/2J vary in sensitivity to a subset of bitter stimuli.	2005 Jun 20	15967025
Haplotypes at the Tas2r locus on distal chromosome 6 vary with quinine taste sensitivity in inbred mice.	2005 Jun 6	15938754
G-protein signaling: back to the future.	2005 Mar	15747061
Characterization of bitter taste responses of intestinal STC-1 cells.	2005 May	15741596
Differential covariation in taste responsiveness to bitter stimuli in rats.	2005 Nov	16267162
Single neurons in the nucleus of the solitary tract respond selectively to bitter taste stimuli.	2006 Nov	16899635
Exploratory behaviour in NO-dependent cyclase mutants of Drosophila shows defects in coincident neuronal signalling.	2007 Aug 6	17683617
Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium.	2007 Jul 25	17595105
Functional characterization of human bitter taste receptors.	2007 May 1	17253962
The neural processing of taste.	2007 Sep 18	17903281
Behavioral genetics and taste.	2007 Sep 18	17903279
Bitter taste receptors influence glucose homeostasis.	2008	19092995
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
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
Gustation in fish: search for prototype of taste perception.	2009	19145412
Chemical analysis and risk assessment of diethyl phthalate in alcoholic beverages with special regard to unrecorded alcohol.	2009 Dec 2	19956573
Bitter-responsive gustatory neurons in the rat parabrachial nucleus.	2009 Mar	19129294
Central Fos expression and conditioned flavor avoidance in rats following intragastric administration of bitter taste receptor ligands.	2009 Mar	19073908
Residual chemosensory capabilities in double P2X2/P2X3 purinergic receptor null mice: intraoral or postingestive detection?	2009 Nov	19833662
A Drosophila gustatory receptor essential for aversive taste and inhibiting male-to-male courtship.	2009 Oct 13	19765987
Discrimination of taste qualities among mouse fungiform taste bud cells.	2009 Sep 15	19622604
Molecular and cellular designs of insect taste receptor system.	2010	20617187
Responses of single chorda tympani taste fibers of the calf (Bos taurus).	2010 Jun	20212013
Vasoactive intestinal peptide-null mice demonstrate enhanced sweet taste preference, dysglycemia, and reduced taste bud leptin receptor expression.	2010 May	20150284
Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction.	2010 Nov	20972434

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 `Fri Dec 15 14:59:22 GMT 2023` Edited by `admin` on `Fri Dec 15 14:59:22 GMT 2023`
Record UNII	4YK5Z54AT2
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

DENATONIUM BENZOATE

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