Basic Info

Common NameCapsaicin(F04799)
2D Structure
Description

Capsaicin 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. (A7835).

FRCD IDF04799
CAS Number404-86-4
PubChem CID1548943
FormulaC18H27NO3
IUPAC Name

(E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methylnon-6-enamide

InChI Key

YKPUWZUDDOIDPM-SOFGYWHQSA-N

InChI

InChI=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+

Canonical SMILES

CC(C)C=CCCCCC(=O)NCC1=CC(=C(C=C1)O)OC

Isomeric SMILES

CC(C)/C=C/CCCCC(=O)NCC1=CC(=C(C=C1)O)OC

WikipediaCapsaicin
Synonyms
        
            Isodecenoic acid vanillylamide
        
            Capsaicin
        
            404-86-4
        
            Zostrix
        
            CAPSAICINE
        
            (E)-Capsaicin
        
            Qutenza
        
            Styptysat
        
            Axsain
        
            E-CAPSAICIN
        
Classifies
                

                  
                    Plant Toxin
                  

                
        
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassBenzenoids
ClassPhenols
SubclassMethoxyphenols
Intermediate Tree NodesNot available
Direct ParentMethoxyphenols
Alternative Parents
Molecular FrameworkAromatic homomonocyclic compounds
SubstituentsMethoxyphenol - 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
DescriptionThis compound belongs to the class of organic compounds known as methoxyphenols. These are compounds containing a methoxy group attached to the benzene ring of a phenol moiety.

Properties

Property NameProperty Value
Molecular Weight305.418
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count3
Rotatable Bond Count9
Complexity341
Monoisotopic Mass305.199
Exact Mass305.199
XLogP3.6
Formal Charge0
Heavy Atom Count22
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count1
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.6219
Human Intestinal AbsorptionHIA+0.9927
Caco-2 PermeabilityCaco2+0.5417
P-glycoprotein SubstrateSubstrate0.6457
P-glycoprotein InhibitorNon-inhibitor0.7854
Inhibitor0.5479
Renal Organic Cation TransporterNon-inhibitor0.8013
Distribution
Subcellular localizationMitochondria0.9272
Metabolism
CYP450 2C9 SubstrateNon-substrate0.7809
CYP450 2D6 SubstrateNon-substrate0.5809
CYP450 3A4 SubstrateSubstrate0.7172
CYP450 1A2 InhibitorInhibitor0.9107
CYP450 2C9 InhibitorInhibitor0.8948
CYP450 2D6 InhibitorInhibitor0.8932
CYP450 2C19 InhibitorNon-inhibitor0.9025
CYP450 3A4 InhibitorInhibitor0.8287
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.7551
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9638
Inhibitor0.6627
AMES ToxicityAMES toxic0.7678
CarcinogensNon-carcinogens0.9153
Fish ToxicityHigh FHMT0.6648
Tetrahymena Pyriformis ToxicityHigh TPT0.9922
Honey Bee ToxicityLow HBT0.5829
BiodegradationNot ready biodegradable0.9069
Acute Oral ToxicityIII0.6676
Carcinogenicity (Three-class)Non-required0.6924

Model Value Unit
Absorption
Aqueous solubility-2.9200LogS
Caco-2 Permeability1.1643LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.2633LD50, mol/kg
Fish Toxicity1.6986pLC50, mg/L
Tetrahymena Pyriformis Toxicity0.5394pIGC50, ug/L

References

TitleJournalDatePubmed ID
Synthesis and characterization of manganese diselenide nanoparticles (MnSeNPs):Determination of capsaicin by using MnSeNP-modified glassy carbon electrode.Mikrochim Acta2018 Jun 229860537
Influence of Fruit Ripening on Color, Organic Acid Contents, Capsaicinoids, AromaCompounds, and Antioxidant Capacity of Shimatogarashi (Capsicum frutescens).J Oleo Sci2018 Jan 129238032
Capsaicin and nonivamide similarly modulate outcome measures of mitochondrialenergy metabolism in HepG2 and 3T3-L1 cells.Food Funct2018 Feb 2129362767
Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neuronsreduces food intake.PLoS Biol2018 Apr 2429689050
Pharyngeal stimulation with sugar triggers local searching behavior inDrosophila.J Exp Biol2017 Sep 1528684466
TRPV4 calcium-permeable channel is a novel regulator of oxidized LDL-inducedmacrophage foam cell formation.Free Radic Biol Med2017 Sep28602913
Toxicity of emerging antifouling biocides to non-target freshwater organisms from three trophic levels.Aquat Toxicol2017 Oct28843204
Nanoencapsulated capsaicin changes migration behavior and morphology of madindarby canine kidney cell monolayers.PLoS One2017 Nov 629107993
Silica nanoparticles inhibit the cation channel TRPV4 in airway epithelial cells.Part Fibre Toxicol2017 Nov 329100528
Antimicrobial Activity of Selected Polyphenols and Capsaicinoids Identified inPepper (Capsicum annuum L.) and Their Possible Mode of Interaction.Curr Microbiol2017 Nov28721659
Capsaicin presynaptically inhibits glutamate release through the activation ofTRPV1 and calcineurin in the hippocampus of rats.Food Funct2017 May 2428418433
Desalted Duck Egg White Peptides Promote Calcium Uptake and Modulate BoneFormation in the Retinoic Acid-Induced Bone Loss Rat and Caco-2 Cell Model.Nutrients2017 May 1228498349
Desalted duck egg white peptides promote calcium uptake by counteracting theadverse effects of phytic acid.Food Chem2017 Mar 1527765248
Deconvoluting physical and chemical heat: Temperature and spiciness influenceflavor differently.Physiol Behav2017 Mar 127988249
Cu Nanoparticles in Hydrogels of Chitosan-PVA Affects the Characteristics ofPost-Harvest and Bioactive Compounds of Jalapeño Pepper.Molecules2017 Jun 228574445
Mechanism of capsaicin inhibition of aldose reductase activity.J Biochem Mol Toxicol2017 Jul28217947
Nonivamide, a capsaicin analogue, exhibits anti-inflammatory properties in peripheral blood mononuclear cells and U-937 macrophages.Mol Nutr Food Res2017 Feb27666931
Sensitive determination of capsaicin in pepper samples using a voltammetricplatform based on carbon nanotubes and ruthenium nanoparticles.Food Chem2017 Aug 128317708
Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminalchemosensory neurons to ethanol and its flavor components.J Neurophysiol2017 Aug 128490641
Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1.Molecules2017 Apr 1928422079

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
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:
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
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
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
Mechanism of Action:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function. Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes. Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana. Not involved in menthol sensation. 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). Activation of cation channels in the membrane of sensory neurons, the so called TRP receptors (TRP = transient receptor potential)
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 ]
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
Mechanism of Action:
The 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.
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 ]