Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C21H29N2O |
| Molecular Weight | 325.4685 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 1 |
SHOW SMILES / InChI
SMILES
CC[N+](CC)(Cc1ccccc1)CC(=Nc2c(C)cccc2C)O
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
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) |
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Target ID: Q9NYV9 Gene ID: 50838.0 Gene Symbol: TAS2R13 Target Organism: Homo sapiens (Human) |
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Target ID: Q9NYW0 Gene ID: 50839.0 Gene Symbol: TAS2R10 Target Organism: Homo sapiens (Human) |
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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: |
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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 |
|---|---|---|
| Bitter substances suppress afferent responses to an appetitive mixture: evidence for peripheral integration of chemosensory stimuli. | 2001 Dec |
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| Covariation in individuals' sensitivities to bitter compounds: evidence supporting multiple receptor/transduction mechanisms. | 2001 Jul |
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| Effect of compound sequence on bitterness enhancement. | 2001 May |
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| Taste receptor cell responses to the bitter stimulus denatonium involve Ca2+ influx via store-operated channels. | 2002 Jun |
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| Rats fail to discriminate quinine from denatonium: implications for the neural coding of bitter-tasting compounds. | 2002 Mar 1 |
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| Partial rescue of taste responses of alpha-gustducin null mice by transgenic expression of alpha-transducin. | 2002 Oct |
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| Stimulation of insulin secretion by denatonium, one of the most bitter-tasting substances known. | 2003 Feb |
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| Comparison of the responses of the chorda tympani and glossopharyngeal nerves to taste stimuli in C57BL/6J mice. | 2003 Mar 4 |
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| A psychophysical investigation of binary bitter-compound interactions. | 2003 May |
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| Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli. | 2003 Oct 29 |
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| Behavioral evidence for a role of alpha-gustducin in glutamate taste. | 2003 Sep |
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| The distinctiveness of ionic and nonionic bitter stimuli. | 2004 Jan |
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| Taste + odor interactions in compound aversion conditioning. | 2004 Nov |
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| Diverse bitter stimuli elicit highly similar patterns of Fos-like immunoreactivity in the nucleus of the solitary tract. | 2004 Sep |
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| In vivo imaging of C. elegans ASH neurons: cellular response and adaptation to chemical repellents. | 2005 Jan 12 |
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| Genomic organization, expression, and function of bitter taste receptors (T2R) in mouse and rat. | 2005 Jul 14 |
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| G-protein signaling: back to the future. | 2005 Mar |
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| Characterization of bitter taste responses of intestinal STC-1 cells. | 2005 May |
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| Differential covariation in taste responsiveness to bitter stimuli in rats. | 2005 Nov |
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| Trpm5 null mice respond to bitter, sweet, and umami compounds. | 2006 Mar |
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| Mouse taste cells with G protein-coupled taste receptors lack voltage-gated calcium channels and SNAP-25. | 2006 Mar 30 |
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| Single neurons in the nucleus of the solitary tract respond selectively to bitter taste stimuli. | 2006 Nov |
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| Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels. | 2006 Oct |
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| Functional characterization of human bitter taste receptors. | 2007 May 1 |
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| Characterization of ligands for fish taste receptors. | 2007 May 23 |
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| 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 |
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| Norepinephrine is coreleased with serotonin in mouse taste buds. | 2008 Dec 3 |
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| The impact of bittering agents on suicidal ingestions of antifreeze. | 2008 Jul |
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| Tonic activity of Galpha-gustducin regulates taste cell responsivity. | 2008 Nov 12 |
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| Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity. | 2008 Nov 13 |
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| Delineation of the chemomechanosensory regulation of gastrin secretion using pure rodent G cells. | 2009 Jul |
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| Central Fos expression and conditioned flavor avoidance in rats following intragastric administration of bitter taste receptor ligands. | 2009 Mar |
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.
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NCI_THESAURUS |
C83486
Created by
admin on Fri Jun 25 22:53:22 UTC 2021 , Edited by admin on Fri Jun 25 22:53:22 UTC 2021
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| Code System | Code | Type | Description | ||
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DENATONIUM
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47324-98-1
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SUB01582MIG
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15488
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1546417
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47324-98-1
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C83659
Created by
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4IK22DF4OU
Created by
admin on Fri Jun 25 22:53:22 UTC 2021 , Edited by admin on Fri Jun 25 22:53:22 UTC 2021
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
