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
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
| 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.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
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
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
Doses
| Dose | Population | Adverse 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... |
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: |
healthy, 34 years n = 1 Health Status: healthy Age Group: 34 years Sex: F Population Size: 1 Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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
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
Edited
Fri Jun 25 23:22:29 UTC 2021
by
admin
on
Fri Jun 25 23:22:29 UTC 2021
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| Record UNII |
0W5171805N
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| Record Status |
Validated (UNII)
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| Record Version |
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C043414
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1674-99-3
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PARENT -> SALT/SOLVATE |
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