Each FAAH inhibitor suppressed the development of paclitaxel-induced neuropathic pain and reduced the maintenance of already established allodynia with sustained efficacy.
Here, we designed dual inhibitors targeting the enzymes FAAH and soluble epoxide hydrolase (sEH), which are targets previously shown to synergize at reducing inflammatory and neuropathic pain.
Fatty acid amide hydrolase (FAAH) represents a potential therapeutic target for number of peripheral and nervous system related disorders including neuropathic pain and neuroinflammation.
Here, we describe dual inhibitors for soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH), two targets known to synergize when treating inflammatory and neuropathic pain.
We compared efficacies of brain-permeant and -impermeant inhibitors of fatty acid amide hydrolase (FAAH) in suppressing neuropathic pain induced by the chemotherapeutic agent paclitaxel.
The investigational compound BIA 10-2474, designed as a long-acting and reversible inhibitor of fatty acid amide hydrolase for the treatment of neuropathic pain, led to the death of one participant and hospitalization of five others due to intracranial hemorrhage in a Phase I clinical trial.