Inhibition of TRPV1 for the treatment of sensitive skin.
During the past years, the topic sensitive skin became one of the most important fields in dermatology. The tremendous interest is based on several studies showing that about 50% of the population declares to have sensitive skin. The human thermoreceptor hTRPV1 was previously identified to contribute to this skin condition while facilitating neurogenic inflammation leading to hyperalgesia. Furthermore, skin sensitivity towards capsaicin, a natural activator of TRPV1, was shown to correlate with sensitive skin. In a screening campaign based on recombinant HEK293-cells stably transfected with hTRPV1, the selective antagonist trans-4-tert-butylcyclohexanol was identified. This antagonist is able to inhibit capsaicin-induced hTRPV1 activation with an IC(50) value of 34 ± 5 μm tested in HEK293-cells as well as in electrophysiological recordings performed in oocytes expressing hTRPV1. Strikingly, in a clinical study with 30 women using topical treatment with o/w emulsions containing 31.6 ppm capsaicin, we were able to show that 0.4% of this inhibitor significantly reduces capsaicin-induced burning (P < 0.0001) in vivo. Thus trans-4-tert-butylcyclohexanol has the potential as a novel bioactive for the treatment of sensitive skin.
Kueper
Thomas
T
Symrise GmbH & Co KG, Mühlenfeldstraße, Holzminden, Germany. Thomas_Kueper@arcor.de
Krohn
Michael
M
Haustedt
Lars Ole
LO
Hatt
Hanns
H
Schmaus
Gerhard
G
Vielhaber
Gabriele
G
D000328:Adult; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D002460:Cell Line; D003511:Cyclohexanols / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D049990:Membrane Transport Modulators / Q000494:pharmacology* / Q000627:therapeutic use*; D009865:Oocytes / Q000187:drug effects; D012678:Sensation Disorders / Q000188:drug therapy*; D012871:Skin Diseases / Q000188:drug therapy*; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014982:Xenopus laevis
D001896:Boron Compounds; D003511:Cyclohexanols; D049990:Membrane Transport Modulators; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C109986:2-aminoethoxydiphenyl borate; C557786:4-tert-butylcyclohexanol; D002211:Capsaicin