Capsazepine
{{chembox
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|verifiedrevid = 443496973
|ImageFile1 = Capsazepine.png
|ImageSize1 = 250px
|ImageFile2 = Capsazepine-3D-balls.png
|PIN = N-[2-(4-Chlorophenyl)ethyl]-7,8-dihydroxy-1,3,4,5-tetrahydro-2H-2-benzazepine-2-carbothioamide
|OtherNames = {{ubl
| N-(4-Chlorophenethyl)-7,8-dihydroxy-1,3,4,5-tetrahydro-2H-benzo[c]azepine-2-carbothioamide
| N-(4-Chlorophenethyl)-7,8-dihydroxy-4,5-dihydro-1H-benzo[c]azepine-2(3H)-carbothioamide
}}
|Section1 = {{Chembox Identifiers
|IUPHAR_ligand = 2461
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID = 2015280
|InChI = 1/C19H21ClN2O2S/c20-16-5-3-13(4-6-16)7-8-21-19(25)22-9-1-2-14-10-17(23)18(24)11-15(14)12-22/h3-6,10-11,23-24H,1-2,7-9,12H2,(H,21,25)
|InChIKey = DRCMAZOSEIMCHM-UHFFFAOYAH
|ChEMBL_Ref = {{ebicite|correct|EBI}}
|ChEMBL = 391997
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI = 1S/C19H21ClN2O2S/c20-16-5-3-13(4-6-16)7-8-21-19(25)22-9-1-2-14-10-17(23)18(24)11-15(14)12-22/h3-6,10-11,23-24H,1-2,7-9,12H2,(H,21,25)
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = DRCMAZOSEIMCHM-UHFFFAOYSA-N
|CASNo_Ref = {{cascite|correct|??}}
|CASNo = 138977-28-3
|PubChem = 2733484
|UNII_Ref = {{fdacite|correct|FDA}}
|UNII = LFW48MY844
|SMILES = Clc1ccc(cc1)CCNC(=S)N3Cc2c(cc(O)c(O)c2)CCC3
}}
|Section2 = {{Chembox Properties
|Formula = C19H21ClN2O2S
|MolarMass = 376.9{{nbsp}}g/mol
}}
}}
Capsazepine is a synthetic antagonist of capsaicin.{{cite journal | vauthors = Bevan S, Hothi S, Hughes G, James IF, Rang HP, Shah K, Walpole CS, Yeats JC | title = Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin | journal = British Journal of Pharmacology | volume = 107 | issue = 2 | pages = 544–52 | date = October 1992 | pmid = 1422598 | pmc = 1907893 | doi = 10.1111/j.1476-5381.1992.tb12781.x }} It is used as a biochemical tool in the study of TRPV ion channels.
Pharmacology
Capsazepine blocks the painful sensation of heat caused by capsaicin (the active ingredient of chilli pepper) which activates the TRPV1 ion channel. Capsazepine is therefore considered to be a TRPV1 antagonist. The TRPV1 channel functions as a pain and temperature sensor in mammalians. Capsazepine blocks the activation of TRPV1 channels by other chemicals, but not by other painful stimuli such as heat. Depending on the pharmacological assay, the IC50 is in the nanomolar to low micromolar range. In addition to its effects on TRPV1 channels, it was also shown to activate the noxious chemical sensor TRPA1 channel,{{cite journal | vauthors = Kistner K, Siklosi N, Babes A, Khalil M, Selescu T, Zimmermann K, Wirtz S, Becker C, Neurath MF, Reeh PW, Engel MA | title = Systemic desensitization through TRPA1 channels by capsazepine and mustard oil - a novel strategy against inflammation and pain | journal = Scientific Reports | volume = 6 | pages = 28621 | date = June 2016 | pmid = 27356469 | pmc = 4928060 | doi = 10.1038/srep28621 | bibcode = 2016NatSR...628621K }} inhibit the cold activated TRPM8 channel,{{cite journal | vauthors = Behrendt HJ, Germann T, Gillen C, Hatt H, Jostock R | title = Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay | journal = British Journal of Pharmacology | volume = 141 | issue = 4 | pages = 737–45 | date = February 2004 | pmid = 14757700 | pmc = 1574235 | doi = 10.1038/sj.bjp.0705652 }} voltage-activated calcium channels{{cite journal | vauthors = Docherty RJ, Yeats JC, Piper AS | title = Capsazepine block of voltage-activated calcium channels in adult rat dorsal root ganglion neurones in culture | journal = British Journal of Pharmacology | volume = 121 | issue = 7 | pages = 1461–7 | date = August 1997 | pmid = 9257928 | pmc = 1564831 | doi = 10.1038/sj.bjp.0701272 }} and nicotinic acetylcholine receptors.{{cite journal | vauthors = Liu L, Simon SA | title = Capsazepine, a vanilloid receptor antagonist, inhibits nicotinic acetylcholine receptors in rat trigeminal ganglia | journal = Neuroscience Letters | volume = 228 | issue = 1 | pages = 29–32 | date = May 1997 | pmid = 9197280 | doi = 10.1016/S0304-3940(97)00358-3 }} It mainly serves as a tool to study the TRPV1 ion channel.{{cite journal | vauthors = Valenzano KJ, Sun Q | title = Current perspectives on the therapeutic utility of VR1 antagonists | journal = Current Medicinal Chemistry | volume = 11 | issue = 24 | pages = 3185–202 | date = December 2004 | pmid = 15579007 | doi = 10.2174/0929867043363686 | url = http://www.bentham-direct.org/pages/content.php?CMC/2004/00000011/00000024/0003C.SGM | url-status = usurped | archive-url = https://archive.today/20130414071145/http://www.bentham-direct.org/pages/content.php?CMC/2004/00000011/00000024/0003C.SGM | archive-date = 2013-04-14 }}
Development
Capsazepine was discovered by a research group working for Novartis. Its synthesis and chemical properties were published in 1994. It was found by modification of the chemical backbone of capsaicin.{{cite journal | vauthors = Walpole CS, Bevan S, Bovermann G, Boelsterli JJ, Breckenridge R, Davies JW, Hughes GA, James I, Oberer L, Winter J | title = The discovery of capsazepine, the first competitive antagonist of the sensory neuron excitants capsaicin and resiniferatoxin | journal = Journal of Medicinal Chemistry | volume = 37 | issue = 13 | pages = 1942–54 | date = June 1994 | pmid = 8027976 | doi = 10.1021/jm00039a006 }}
Use in biotechnology
By incorporation of an azobenzene unit, a photoswitchable version of capsazepine (AC4) was developed in 2013 that allows for optical control of TRPV1 channels with light.{{cite journal | vauthors = Stein M, Breit A, Fehrentz T, Gudermann T, Trauner D | title = Optical control of TRPV1 channels | journal = Angewandte Chemie | volume = 52 | issue = 37 | pages = 9845–8 | date = September 2013 | pmid = 23873837 | doi = 10.1002/anie.201302530 }}[http://www.en.uni-muenchen.de/news/newsarchiv/2013/f-m-55-13.html Optical switches: Putting the fire out with light] LMU Munich, 07/25/2013