Tmic
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Record Information
Version2.0
Creation Date2009-07-23 18:26:09 UTC
Update Date2014-12-24 20:25:57 UTC
Accession NumberT3D3085
Identification
Common NameCapsaicin
ClassSmall Molecule
DescriptionCapsaicin is identified as the primary pungent principle in Capsicum fruits. Hot chili peppers that belong to the plant genus Capsicum (family Solanaceae) are among the most heavily consumed spices throughout the world. The capsaicin content of green and red peppers ranges from 0.1 to 1%. Capsaicin evokes numerous biological effects and thus has been the target of extensive., investigations since its initial identification in 1919. One of the most recognized physiological properties of capsaicin is its selective effects on the peripheral part of the sensory nervous system, particularly on the primary afferent neurons. The compound is known to deplete the neurotransmitter of painful impulses known as substance P from the sensory nerve terminals, which provides a rationale for its use as a versatile experimental tool for studying pain mechanisms and also for pharmacotherapy to treat some peripheral painful states, such as rheumatoid arthritis, post-herpetic neuralgia, post-mastectomy pain syndrome and diabetic neuropathy. Considering the frequent consumption of capsaicin as a food additive and its current therapeutic application, correct assessment of any harmful effects of this compound is important from the public health standpoint. Ingestion of large amounts of capsaicin has been reported to cause histopathological and biochemical changes, including erosion of gastric mucosa and hepatic necrosis. However, there are contradictory data on the mutagenicity of capsaicin. A recent epidemiological study conducted in Mexico revealed that consumers of chili pepper were at higher risk for gastric cancer than non-consumers. However, it remains unclear whether capsaicin present in hot chili pepper is a major causative factor in the aetiology of gastric cancer in humans. A growing number of recent studies have focused on anticarcinogenic or antimutagenic phytochemicals, particularly those included in human diet. In summary, capsaicin has dual effects on chemically induced carcinogenesis and mutagenesis. Although a minute amount of capsaicin displays few or no deleterious effects, heavy ingestion of the compound has been associated with necrosis, ulceration and even carcinogenesis. Capsaicin is considered to be metabolized by cytochrome P-450-dependent mixed-function oxidases to reactive species. (1).
Compound Type
  • Amide
  • Amine
  • Ether
  • Food Toxin
  • Household Toxin
  • Lachrymator
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
Synonyms
Synonym
(E)-8-Methyl-N-vanillyl-6-nonenamide(8cl)
(E)8-methyl-N-vanillyl-6-Nonenamide
Axsain
E-Capsaicin
epsilon-Capsaicin
Isodecenoate
Isodecenoic acid
Isodecenoic acid vanillylamide
N-(4-Hydroxy-3-methoxybenzyl)-8-methylnon-trans-6-enamide
Styptysat
trans-8-Methyl-N-vanillyl-6-nonenamide
Transacin
Zostrix
Chemical FormulaC18H27NO3
Average Molecular Mass305.412 g/mol
Monoisotopic Mass305.199 g/mol
CAS Registry Number404-86-4
IUPAC Name(6E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methylnon-6-enamide
Traditional Namecapsaicin
SMILES[H]\C(CCCCC(O)=NCC1=CC(OC)=C(O)C=C1)=C(\[H])C(C)C
InChI IdentifierInChI=1S/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+
InChI KeyInChIKey=YKPUWZUDDOIDPM-SOFGYWHQSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as methoxyphenols. Methoxyphenols are compounds containing a methoxy group attached to the benzene ring of a phenol moiety.
KingdomOrganic compounds
Super ClassBenzenoids
ClassPhenols
Sub ClassMethoxyphenols
Direct ParentMethoxyphenols
Alternative Parents
Substituents
  • Methoxyphenol
  • Phenoxy compound
  • Anisole
  • Methoxybenzene
  • Phenol ether
  • Alkyl aryl ether
  • 1-hydroxy-2-unsubstituted benzenoid
  • Monocyclic benzene moiety
  • Fatty acyl
  • Fatty amide
  • N-acyl-amine
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Carboxylic acid derivative
  • Ether
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point65°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0084 g/LALOGPS
logP3.8ALOGPS
logP3.75ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)9.93ChemAxon
pKa (Strongest Basic)-0.52ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.56 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity90.32 m³·mol⁻¹ChemAxon
Polarizability36.32 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-052o-9860000000-4151cd60d08276e5122aView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-03mi-9576000000-fb9f159d71790f546865View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-014i-0901000000-adba1bb6f254087febe8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITTOF , negativesplash10-014i-0900000000-5be0e66854b20d7a5a03View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-014i-0900000000-4337ff26dcbd2a77725eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-014i-0900000000-c94a246143850aa73e44View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-014r-0950000000-3d145ef428e054b3e535View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-014r-0950000000-c3ca097a6480ab798ff3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0900000000-4e8f98d1f848f30117d7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-000i-0900000000-58fab2fdd15893ea71e7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-000i-0900000000-296a0cb1555da4f1ccd7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-03di-0209000000-a91e6403d5a0c0b67c2eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-03di-0209000000-dd0879d3f4f3a8b022c3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-014i-0149000000-d6a9f6e70ae7cd7aec38View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-014i-0149000000-6fcf63c3bf44a4efc5bdView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-06sl-0075690000-b562b766019cc7cbd98fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-01x3-0094560000-f354077f4cd51e45b945View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-004i-0002900000-ce1ea9819252343543cdView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-004i-0002911000-6c37470f794c89a66410View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-000i-0900000000-00619747b8012ce6aa64View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-000i-0900000000-3ca73f5212a7643b45d2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0912000000-95e090cebb8f95d7fe89View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-0900000000-6fb8b34936b848190c39View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0f79-4900000000-ade1e8ba842adf972c83View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0419000000-80bfd538da9be3f08fe0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-0922000000-00b0b7b3e9df2464d425View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-7900000000-8b112ae03b8d84d338f3View in MoNA
Toxicity Profile
Route of ExposureOral (ingestion) (6) ; dermal (6)
Mechanism of ToxicityThe burning and painful sensations associated with capsaicin result from its chemical interaction with sensory neurons. Capsaicin, as a member of the vanilloid family, binds to the vanilloid receptor 1 (VR1). VR1 permits cations to pass through the cell membrane and into the cell when activated. The resulting depolarization of the neuron stimulates it to signal the brain. By binding to the VR1 receptor, the capsaicin molecule produces the same sensation that excessive heat or abrasive damage would cause, explaining why the spiciness of capsaicin is described as a burning sensation. (5)
MetabolismNot Available
Toxicity ValuesLD50: 47200 ug/kg (Oral, Mouse) (4) LD50: 6500 ug/kg (Intraperitoneal, Mouse) (4) LD50: 9000 ug/kg (Subcutaneous, Mouse) (4) LD50: 400 ug/kg (Intravenous, Mouse) (4) LD50: 7800 ug/kg (Intramuscular, Mouse) (4) LD50: 1600 ug/kg (Intratracheal, Mouse) (4)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC.
Uses/SourcesCapsaicin is the active component of chili peppers (genus Capsicum). It is a powerful irritant that is commonly used in food products to give them added spice. Capsaicin is also used in topical ointments to relieve the pain of peripheral neuropathy and can be found in pepper spray. (5)
Minimum Risk LevelNot Available
Health EffectsCapsaicin is a powerful irritant and severe over-exposure can result in death. (5)
SymptomsCapsaicin is a powerful irritant and causes burning or stinging pain to the skin. Ingestion of large amounts can cause nausea, vomiting, abdominal pain and burning diarrhea. Eye exposure produces intense tearing, pain, conjunctivitis and blepharospasm. (5)
TreatmentCapsaicin should be washed off the skin using soap, shampoo, or other detergents, or rubbed off with oily compounds such as vegetable oil, paraffin oil, petroleum jelly, creams, or polyethylene glycol. Burning and pain symptoms can be effectively relieved by cooling from ice, cold water, cold surfaces, or a flow of air. In severe cases, eye burn might be treated symptomatically with topical ophthalmic anaesthetics, while mucous membrane burn can be treated with lidocaine gel. Capsaicin-induced asthma might be treated with nebulized bronchodilators or oral antihistamines or corticosteroids. (5)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB02227
PubChem Compound ID1548943
ChEMBL IDCHEMBL294199
ChemSpider ID1265957
KEGG IDC06866
UniProt IDNot Available
OMIM ID
ChEBI ID3374
BioCyc IDCAPSAICIN
CTD IDNot Available
Stitch IDCapsaicin
PDB IDNot Available
ACToR ID244
Wikipedia LinkCapsaicin
References
Synthesis ReferenceGannett, Peter M.; Nagel, Donald L.; Reilly, Pam J.; Lawson, Terence; Sharpe, Jody; Toth, Bela. Capsaicinoids: their separation, synthesis, and mutagenicity. Journal of Organic Chemistry (1988), 53(5), 1064-71.
MSDSLink
General References
  1. Surh YJ, Lee SS: Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen? Food Chem Toxicol. 1996 Mar;34(3):313-6. [8621114 ]
  2. Akopian AN, Ruparel NB, Jeske NA, Hargreaves KM: Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization. J Physiol. 2007 Aug 15;583(Pt 1):175-93. Epub 2007 Jun 21. [17584831 ]
  3. Simpson DM, Estanislao L, Brown SJ, Sampson J: An open-label pilot study of high-concentration capsaicin patch in painful HIV neuropathy. J Pain Symptom Manage. 2008 Mar;35(3):299-306. Epub 2007 Oct 23. [17959343 ]
  4. Lewis RJ Sr. (ed) (2004). Sax's Dangerous Properties of Industrial Materials. 11th Edition. Hoboken, NJ: Wiley-Interscience, Wiley & Sons, Inc.
  5. Wikipedia. Capsaicin. Last Updated 16 July 2009. [Link]
  6. Wikipedia. Phytotoxin. Last Updated 7 August 2009. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Cannabinoid receptor activity
Specific Function:
Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.
Gene Name:
CNR2
Uniprot ID:
P34972
Molecular Weight:
39680.275 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 86537
References
  1. Appendino G, De Petrocellis L, Trevisani M, Minassi A, Daddario N, Moriello AS, Gazzieri D, Ligresti A, Campi B, Fontana G, Pinna C, Geppetti P, Di Marzo V: Development of the first ultra-potent "capsaicinoid" agonist at transient receptor potential vanilloid type 1 (TRPV1) channels and its therapeutic potential. J Pharmacol Exp Ther. 2005 Feb;312(2):561-70. Epub 2004 Sep 8. [15356216 ]
  2. Appendino G, Ligresti A, Minassi A, Cascio MG, Allara M, Taglialatela-Scafati O, Pertwee RG, De Petrocellis L, Di Marzo V: Conformationally constrained fatty acid ethanolamides as cannabinoid and vanilloid receptor probes. J Med Chem. 2009 May 14;52(9):3001-9. doi: 10.1021/jm900130m. [19361197 ]
General Function:
Transmembrane signaling receptor activity
Specific Function:
Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis (By similarity). Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel.
Gene Name:
TRPV1
Uniprot ID:
Q8NER1
Molecular Weight:
94955.33 Da
References
  1. Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, Moriello AS, Davis JB, Mechoulam R, Di Marzo V: Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. 2001 Oct;134(4):845-52. [11606325 ]
  2. Wikipedia. Capsaicin. Last Updated 16 July 2009. [Link]
General Function:
Drug binding
Specific Function:
Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered ligand binding.
Gene Name:
CNR1
Uniprot ID:
P21554
Molecular Weight:
52857.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 20461
References
  1. Appendino G, Ligresti A, Minassi A, Cascio MG, Allara M, Taglialatela-Scafati O, Pertwee RG, De Petrocellis L, Di Marzo V: Conformationally constrained fatty acid ethanolamides as cannabinoid and vanilloid receptor probes. J Med Chem. 2009 May 14;52(9):3001-9. doi: 10.1021/jm900130m. [19361197 ]
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells.
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC503.8 uMNot AvailableBindingDB 20461
References
  1. Larsson J, Gottfries J, Bohlin L, Backlund A: Expanding the ChemGPS chemical space with natural products. J Nat Prod. 2005 Jul;68(7):985-91. [16038536 ]
General Function:
Temperature-gated cation channel activity
Specific Function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular Weight:
127499.88 Da
References
  1. Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]
  2. Lachrymation [Link]