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,[2] inhibit the cold activated TRPM8 channel,[3]voltage-activated calcium channels[4] and nicotinic acetylcholine receptors.[5] It mainly serves as a tool to study the TRPV1 ion channel.[6]
Developmentedit
Capsazepine was discovered by a research group working for Novartis.[1] Its synthesis and chemical properties were published in 1994. It was found by modification of the chemical backbone of capsaicin.[7]
Use in biotechnologyedit
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.[8][9]
^ abBevan S, Hothi S, Hughes G, James IF, Rang HP, Shah K, Walpole CS, Yeats JC (October 1992). "Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin". British Journal of Pharmacology. 107 (2): 544–52. doi:10.1111/j.1476-5381.1992.tb12781.x. PMC1907893. PMID 1422598.
^Kistner K, Siklosi N, Babes A, Khalil M, Selescu T, Zimmermann K, Wirtz S, Becker C, Neurath MF, Reeh PW, Engel MA (June 2016). "Systemic desensitization through TRPA1 channels by capsazepine and mustard oil - a novel strategy against inflammation and pain". Scientific Reports. 6: 28621. doi:10.1038/srep28621. PMC4928060. PMID 27356469.
^Behrendt HJ, Germann T, Gillen C, Hatt H, Jostock R (February 2004). "Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay". British Journal of Pharmacology. 141 (4): 737–45. doi:10.1038/sj.bjp.0705652. PMC1574235. PMID 14757700.
^Docherty RJ, Yeats JC, Piper AS (August 1997). "Capsazepine block of voltage-activated calcium channels in adult rat dorsal root ganglion neurones in culture". British Journal of Pharmacology. 121 (7): 1461–7. doi:10.1038/sj.bjp.0701272. PMC1564831. PMID 9257928.
^Liu L, Simon SA (May 1997). "Capsazepine, a vanilloid receptor antagonist, inhibits nicotinic acetylcholine receptors in rat trigeminal ganglia". Neuroscience Letters. 228 (1): 29–32. doi:10.1016/S0304-3940(97)00358-3. PMID 9197280.
^Valenzano KJ, Sun Q (December 2004). "Current perspectives on the therapeutic utility of VR1 antagonists". Current Medicinal Chemistry. 11 (24): 3185–202. doi:10.2174/0929867043363686. PMID 15579007. Archived from the original on 2013-04-14.
^Walpole CS, Bevan S, Bovermann G, Boelsterli JJ, Breckenridge R, Davies JW, Hughes GA, James I, Oberer L, Winter J (June 1994). "The discovery of capsazepine, the first competitive antagonist of the sensory neuron excitants capsaicin and resiniferatoxin". Journal of Medicinal Chemistry. 37 (13): 1942–54. doi:10.1021/jm00039a006. PMID 8027976.
^Stein M, Breit A, Fehrentz T, Gudermann T, Trauner D (September 2013). "Optical control of TRPV1 channels". Angewandte Chemie. 52 (37): 9845–8. doi:10.1002/anie.201302530. PMID 23873837.
^Optical switches: Putting the fire out with light LMU Munich, 07/25/2013
January 01, 1970
capsazepine, synthetic, antagonist, capsaicin, used, biochemical, tool, study, trpv, channels, names, preferred, iupac, name, chlorophenyl, ethyl, dihydroxy, tetrahydro, benzazepine, carbothioamide, other, names, chlorophenethyl, dihydroxy, tetrahydro, benzo, . Capsazepine is a synthetic antagonist of capsaicin 1 It is used as a biochemical tool in the study of TRPV ion channels Capsazepine Names Preferred IUPAC name N 2 4 Chlorophenyl ethyl 7 8 dihydroxy 1 3 4 5 tetrahydro 2H 2 benzazepine 2 carbothioamide Other names N 4 Chlorophenethyl 7 8 dihydroxy 1 3 4 5 tetrahydro 2H benzo c azepine 2 carbothioamideN 4 Chlorophenethyl 7 8 dihydroxy 4 5 dihydro 1H benzo c azepine 2 3H carbothioamide Identifiers CAS Number 138977 28 3 Y 3D model JSmol Interactive image ChEMBL ChEMBL391997 Y ChemSpider 2015280 Y IUPHAR BPS 2461 PubChem CID 2733484 UNII LFW48MY844 Y CompTox Dashboard EPA DTXSID20160852 InChI InChI 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 YKey DRCMAZOSEIMCHM UHFFFAOYSA N YInChI 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 Key DRCMAZOSEIMCHM UHFFFAOYAH SMILES Clc1ccc cc1 CCNC S N3Cc2c cc O c O c2 CCC3 Properties Chemical formula C19H21ClN2O2S Molar mass 376 9 g mol Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Y verify what is Y N Infobox references Contents 1 Pharmacology 2 Development 3 Use in biotechnology 4 See also 5 ReferencesPharmacology editCapsazepine 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 2 inhibit the cold activated TRPM8 channel 3 voltage activated calcium channels 4 and nicotinic acetylcholine receptors 5 It mainly serves as a tool to study the TRPV1 ion channel 6 Development editCapsazepine was discovered by a research group working for Novartis 1 Its synthesis and chemical properties were published in 1994 It was found by modification of the chemical backbone of capsaicin 7 Use in biotechnology editBy 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 8 9 See also editDiscovery and development of TRPV1 antagonists Menthol Herkinorin JWH 133References edit a b Bevan S Hothi S Hughes G James IF Rang HP Shah K Walpole CS Yeats JC October 1992 Capsazepine a competitive antagonist of the sensory neurone excitant capsaicin British Journal of Pharmacology 107 2 544 52 doi 10 1111 j 1476 5381 1992 tb12781 x PMC 1907893 PMID 1422598 Kistner K Siklosi N Babes A Khalil M Selescu T Zimmermann K Wirtz S Becker C Neurath MF Reeh PW Engel MA June 2016 Systemic desensitization through TRPA1 channels by capsazepine and mustard oil a novel strategy against inflammation and pain Scientific Reports 6 28621 doi 10 1038 srep28621 PMC 4928060 PMID 27356469 Behrendt HJ Germann T Gillen C Hatt H Jostock R February 2004 Characterization of the mouse cold menthol receptor TRPM8 and vanilloid receptor type 1 VR1 using a fluorometric imaging plate reader FLIPR assay British Journal of Pharmacology 141 4 737 45 doi 10 1038 sj bjp 0705652 PMC 1574235 PMID 14757700 Docherty RJ Yeats JC Piper AS August 1997 Capsazepine block of voltage activated calcium channels in adult rat dorsal root ganglion neurones in culture British Journal of Pharmacology 121 7 1461 7 doi 10 1038 sj bjp 0701272 PMC 1564831 PMID 9257928 Liu L Simon SA May 1997 Capsazepine a vanilloid receptor antagonist inhibits nicotinic acetylcholine receptors in rat trigeminal ganglia Neuroscience Letters 228 1 29 32 doi 10 1016 S0304 3940 97 00358 3 PMID 9197280 Valenzano KJ Sun Q December 2004 Current perspectives on the therapeutic utility of VR1 antagonists Current Medicinal Chemistry 11 24 3185 202 doi 10 2174 0929867043363686 PMID 15579007 Archived from the original on 2013 04 14 Walpole CS Bevan S Bovermann G Boelsterli JJ Breckenridge R Davies JW Hughes GA James I Oberer L Winter J June 1994 The discovery of capsazepine the first competitive antagonist of the sensory neuron excitants capsaicin and resiniferatoxin Journal of Medicinal Chemistry 37 13 1942 54 doi 10 1021 jm00039a006 PMID 8027976 Stein M Breit A Fehrentz T Gudermann T Trauner D September 2013 Optical control of TRPV1 channels Angewandte Chemie 52 37 9845 8 doi 10 1002 anie 201302530 PMID 23873837 Optical switches Putting the fire out with light LMU Munich 07 25 2013 Retrieved from https en wikipedia org w index php title Capsazepine amp oldid 1194222035, wikipedia, wiki, book, books, library,
