Pharmacology of TRP channels

Abstract

TRP channels are a family of ion channels involved in a plethora of physiological sensory processes. Since their discovery they have attracted the attention of academic and non-academic laboratories with the aim of developing modulators that could be used as pharmacological tools for unveiling their physiological and pathological activities, and as therapeutic compounds for intervening in TRP dysfunction. Intriguingly, TRP pharmacology shows dispersed progress, with vast pharmacology developed for some members of the so-called thermoTRP channel subfamily (TRPV1, TRPV3, TRPM8 and TRPA1), and very little, for all other TRP channels. Pharmacologically, the most investigated TRP channel is undoubtedly TRPV1 for which a large number of agonists and antagonists with in vitro and in vivo activities have been characterized. Recent interest has grown for TRPV3, TRPM8 and TRPA1 because of their implication in several human pathologies and disorders. Similarly, the TRPM3 channel is emerging as important targets for pain transduction. With the development of novel screening methods, the focus is slowly changing to other TRP members for whom we do not have appropriate agonists or antagonists. These include the TRPC family, which has limited our understanding of their role in pathological processes and whether pharmacological intervention in these channels will have a therapeutic benefit. A bright future is anticipated for TRP pharmacology, with the discovery of selective and potent modulators for this important family of sensory channels.