Overview
Alomone Labs A-889425 inhibits capsaicin activated TRPV1 channels heterologously expressed in C-6 cells.Cells were loaded with Fluo-3 AM and changes in intracellular Ca2+ were measured. Normalized fluorescence before (control, gray dotted line) and after application of 1µM capsaicin (#C-125) (black lines) in cells pre-incubated without or with 0.5 µM A-889425 (#A-195) (top and bottom lines, as indicated). 10 min pre-incubation with 0.5 µM A-889425 abolishes capsaicin-evoked rise in intracellular Ca2+.
TRPV1 (transient receptor potential vanilloid family type 1) channels are activated and/or modulated by noxious heat, capsaicin, protons and other endogenous agents released following tissue injury.
A-889425 is a selective and competitive TRPV1 channel blocker with an IC50 of 335 nM to displace capsaicin at rat receptors, and has good penetration into the CNS1. In the somatic sensory system, receptor-selective TRPV1 antagonists, such as A-889425, attenuate mechanical hyperalgesia in models of inflammatory, osteoarthritic, and neuropathic pain2. Administration of A-889425 inhibited mechanically evoked activity of wide dynamic range (WDR) neurons in the rat spinal dorsal horn under conditions of peripheral inflammation but not in uninjured rats1.
In addition to actions on the nociceptive system, several TRPV1 blockers like A-889425 have been reported to affect thermoregulation by transiently raising core body temperature following systemic administration in both animals and humans3.
