Unknown

Dataset Information

0

Orally Available Soluble Epoxide Hydrolase/Phosphodiesterase 4 Dual Inhibitor Treats Inflammatory Pain.


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 ( Tmax = 30 min; Cmax = 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.

SUBMITTER: Blocher R 

PROVIDER: S-EPMC5933862 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC3064364 | BioStudies
2011-01-01 | S-EPMC3281519 | BioStudies
2018-01-01 | S-EPMC6210075 | BioStudies
2018-01-01 | S-EPMC5837813 | BioStudies
2013-01-01 | S-EPMC3578047 | BioStudies
2015-01-01 | S-EPMC4666679 | BioStudies
2014-01-01 | S-EPMC4148150 | BioStudies
2014-01-01 | S-EPMC4150748 | BioStudies
2013-01-01 | S-EPMC3733540 | BioStudies
2017-01-01 | S-EPMC5317001 | BioStudies