Referenced in: none

Automatically associated channels: TRP , TRPA , TRPA1 , TRPM , TRPM8 , TRPV , TRPV1

Title: Inhibitory effect of positively charged triazine antagonists of prokineticin receptors on the transient receptor vanilloid type-1 (TRPV1) channel.

Authors: Luciano De Petrocellis, Aniello Schiano Moriello, Joon Seok Byun, Joo Mi Sohn, Jae Yeol Lee, Ana Vázquez-Romero, Maria Garrido, Angel Messeguer, Fang-Xiong Zhang, Gerald W Zamponi, Alessandro Deplano, Cenzo Congiu, Valentina Onnis, Gianfranco Balboni, Vincenzo Di Marzo

Journal, date & volume: Pharmacol. Res., 2015 Sep , 99, 362-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26192347

Abstract
Four positively charged compounds, previously shown to produce analgesic activity by interacting with prokineticin receptor or T-type calcium channels, were tested for their ability to inhibit capsaicin-induced elevation of intracellular Ca(2+) in HEK-293 cells stably transfected with the human recombinant TRPV1, with the goal of identifying novel TRPV1 open-pore inhibitors. KYS-05090 showed the highest potency as a TRPV1 antagonist, even higher than that of the open-pore triazine inhibitor 8aA. The latter showed quite remarkable agonist/desensitizer activity at the rat recombinant TRPM8 channel. The activity of KYS-05090 and the other compounds was selective because none of these compounds was able to modulate the rat TRPA1 channel. Open-pore inhibitors of TRPV1 may be a new class of multi-target analgesics with lesser side effects, such as loss of acute pain sensitivity and hyperthermia, than most TRPV1 antagonists developed so far.