Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C21H29N2O.C2H3O2.H2O |
| Molecular Weight | 402.5271 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O.CC([O-])=O.CC[N+](CC)(CC(=O)NC1=C(C)C=CC=C1C)CC2=CC=CC=C2
InChI
InChIKey=GNXLNAUMSDPCGP-UHFFFAOYSA-N
InChI=1S/C21H28N2O.C2H4O2.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;1-2(3)4;/h7-14H,5-6,15-16H2,1-4H3;1H3,(H,3,4);1H2
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 |
|---|---|---|
| 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 |
|
| 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 |
|
| Taste receptor cell responses to the bitter stimulus denatonium involve Ca2+ influx via store-operated channels. | 2002 Jun |
|
| Stimulation of insulin secretion by denatonium, one of the most bitter-tasting substances known. | 2003 Feb |
|
| Taste + odor interactions in compound aversion conditioning. | 2004 Nov |
|
| Umami taste responses are mediated by alpha-transducin and alpha-gustducin. | 2004 Sep 1 |
|
| 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 |
|
| PLCbeta2-independent behavioral avoidance of prototypical bitter-tasting ligands. | 2005 Sep |
|
| Mouse taste cells with G protein-coupled taste receptors lack voltage-gated calcium channels and SNAP-25. | 2006 Mar 30 |
|
| Single neurons in the nucleus of the solitary tract respond selectively to bitter taste stimuli. | 2006 Nov |
|
| Behavioral genetics and taste. | 2007 Sep 18 |
|
| Norepinephrine is coreleased with serotonin in mouse taste buds. | 2008 Dec 3 |
|
| The impact of bittering agents on suicidal ingestions of antifreeze. | 2008 Jul |
|
| The taste transduction channel TRPM5 is a locus for bitter-sweet taste interactions. | 2008 May |
|
| 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 |
|
| 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 |
|
| Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. | 2010 Nov |
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.
| Name | Type | Language | ||
|---|---|---|---|---|
|
Common Name | English | ||
|
Common Name | English |
| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
|
FDA ORPHAN DRUG |
942123
Created by
admin on Sat Dec 16 16:35:27 GMT 2023 , Edited by admin on Sat Dec 16 16:35:27 GMT 2023
|
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
YE84H43CRF
Created by
admin on Sat Dec 16 16:35:27 GMT 2023 , Edited by admin on Sat Dec 16 16:35:27 GMT 2023
|
PRIMARY | |||
|
168429466
Created by
admin on Sat Dec 16 16:35:27 GMT 2023 , Edited by admin on Sat Dec 16 16:35:27 GMT 2023
|
PRIMARY |
ACTIVE MOIETY
SUBSTANCE RECORD
