Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Nobilamides A-H, long-acting transient receptor potential vanilloid-1 (TRPV1) antagonists from mollusk-associated bacteria.

Authors: Zhenjian Lin, Christopher A Reilly, Rowena Antemano, Ronald W Hughen, Lenny Marett, Gisela P Concepcion, Margo G Haygood, Baldomero M Olivera, Alan Light, Eric W Schmidt

Journal, date & volume: J. Med. Chem., 2011 Jun 9 , 54, 3746-55

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21524089

Abstract
New compounds nobilamides A-H and related known compounds A-3302-A and A-3302-B were isolated based upon their suppression of capsaicin-induced calcium uptake in a mouse dorsal root ganglion primary cell culture assay. Two of these compounds, nobilamide B and A-3302-A, were shown to be long-acting antagonists of mouse and human TRPV1 channels, abolishing activity for >1 h after removal of drug presumably via a covalent attachment. Other derivatives also inhibited the TRPV1 channel, albeit with low potency, affording a structure-activity profile to support the proposed mechanism of action. While the activities were modest, we propose a new mechanism of action and a new site of binding for these inhibitors that may spur development of related analogues for treatment of pain.