Inhibition of soluble epoxide hydrolase as a novel approach to high dose diazepam induced hypotension.

ABSTRACT:

Context

Hypotension is one of the dose limiting side effects of benzodiazepines (BZDs), in particular of diazepam (DZP) which is still widely used in the clinic. Currently, only one FDA approved antidote exists for BZD overdose and novel approaches are needed to improve management of DZP overdose, dependency and withdrawal.

Objective

Here, we hypothesized that increasing bioactive lipid mediators termed epoxy fatty acids (EpFAs) will prevent hypotension, as was shown previously in a murine model of LPS-induced hypotension. Therefore, we first characterized the time and dose dependent profile of DZP induced hypotension in mice, and then investigated the reversal of the hypotensive effect by inhibiting the soluble epoxide hydrolase (sEH), an enzyme that regulates the levels of

SUBMITTER: Ulu A 

PROVIDER: S-EPMC5328659 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature