The TRPV1 Channel Modulator Imidazo[1,2-a]Indole Derivative Exhibits Pronounced and Versatile Anti-Inflammatory...

Background: Recently, data have been published about the inhibitory effect at low nanomolar concentrations on the TRPV1 ion channel for a new indole derivative named SV-1010. This molecule has also been shown to have a strong analgesic effect in mice and rats. Since the biological target of SV-1010 is the TRPV1 ion channel, which plays an active role in inflammation, we conducted a series of animal tests to evaluate its potential as an anti-inflammatory agent. Methods: Nine different inflammatory agents were used to assess acute inflammation, and diclofenac was chosen as a positive control. Additionally SV-1010 effects in chronic proliferative and immunogenic inflammation models were also measured. Results: SV-1010 demonstrated a significant effect in most inflammatory tests, often surpassing that of diclofenac, and showed comparable efficacy to several other recognized anti-inflammatory drugs under certain conditions. The level of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, exceeded after LPS administration was normalized to the non-LPS control group level by a dose of 0.1 mg/kg of SV-1010, and the effect was comparable to that of diclofenac at a dose of 12.5 mg/kg. The estimation by qPCR of the content of two enzymes, COX-2 and iNOS, which were increased by 10.8- and 19.4-fold, respectively, after LPS induction showed different molecular targets being utilized, manifested in the normalization of COX-2 content only after diclofenac treatment, and iNOS content only after SV-1010 treatment. Conclusions: Due to the simplicity of synthesis and low effective dose for mammal treatment, this compound can be interesting for a practice.