Evaluation of analgesic and anti-inflammatory activity of purine-2,6-dione-based TRPA1 antagonists with PDE4/7 inhibitory activity.

ABSTRACT:

Background

To verify the validity of the proposed pain treatment approach, which is based on concomitant blocking of the Transient Receptor Potential Ankyrin 1 (TRPA1) channel and phosphodiesterases (PDEs) 4B/7A activity, we continued our pharmacological studies on 8-alkoxypurine-2,6-diones selected based on previous in vitro screening.

Methods

Derivatives 17, 31, and 36 were pharmacologically evaluated in vivo using the formalin test and oxaliplatin-induced neuropathic pain: the von Frey and the cold plate tests, and in the carrageenan-induced edema model. Compound 36, which turned out to be the most promising, was further evaluated in the collagen-induced arthritis model. The pharmacokinetic parameters of this compound were also estimated.

Results

All the tested com

SUBMITTER: Zygmunt M 

PROVIDER: S-EPMC9584878 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature