AI Article Synopsis
- - The study focused on developing new dual inhibitors targeting soluble epoxide hydrolase (sEH) and phosphodiesterase 4 (PDE4), resulting in 21 novel compounds with effective outcomes in preliminary tests.
- - Among these compounds, MPPA was identified as a promising bioavailable option, showing rapid absorption and significant pain-reducing effects in a rat model after oral administration.
- - Notably, MPPA did not impact the self-motivated behavior of rats nor their pain response time in control situations, suggesting minimal side effects on normal activities.
Article Abstract
Inspired by previously discovered enhanced analgesic efficacy between soluble epoxide hydrolase (sEH) and phosphodiesterase 4 (PDE4) inhibitors, we designed, synthesized and characterized 21 novel sEH/PDE4 dual inhibitors. The best of these displayed good efficacy in in vitro assays. Further pharmacokinetic studies of a subset of four selected compounds led to the identification of a bioavailable dual inhibitor N-(4-methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (MPPA). In a lipopolysaccharide induced inflammatory pain rat model, MPPA rapidly increased in the blood ( T = 30 min; C = 460 nM) after oral administration of 3 mg/kg and reduced inflammatory pain with rapid onset of action correlating with blood levels over a time course of 4 h. Additionally, MPPA does not alter self-motivated exploration of rats with inflammatory pain or the withdrawal latency in control rats.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933862 | PMC |
| http://dx.doi.org/10.1021/acs.jmedchem.7b01804 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!