TRPV1 Ligands with Hyperthermic, Hypothermic and No Temperature Effects in Rats

Overview

Journal Temperature (Austin)

Date 2016 May 27

PMID 27227030

Citations 13

Authors

Arthur Gomtsyan

Heath A McDonald

Robert G Schmidt

Jerome F Daanen

Eric A Voight

Jason A Segreti

Pamela S Puttfarcken

Regina M Reilly

Michael E Kort

Michael J Dart

Philip R Kym

Affiliations

Soon will be listed here.

Abstract

Transient receptor potential vanilloid 1 (TRPV1) is a multifunctional ion channel playing important roles in a numerous biological processes including the regulation of body temperature. Within distinct and tight chemical space of chromanyl ureas TRPV1 ligands were identified that exhibit distinctive pharmacology and a spectrum of thermoregulatory effects ranging from hypothermia to hyperthermia. The ability to manipulate these effects by subtle structural modifications of chromanyl ureas may serve as a productive approach in TRPV1 drug discovery programs addressing either side effect or desired target profiles of the compounds. Because chromanyl ureas in the TRPV1 context are generally antagonists, we verified observed partial agonist effects of a subset of compounds within that chemotype by comparing the in vitro profile of Compound 3 with known partial agonist 5'-I-RTX.

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