Advances in the discovery of fatty acid amide hydrolase inhibitors: what does the future hold?

Abstract

Introduction: Fatty acid amide hydrolase (FAAH) is a membrane-bound enzyme, that inactivates endogenous signaling lipids of the fatty acid amide family, including the endocannabinoid anandamide (N-arachidonoylethanolamine, AEA). The latter compound has been shown to regulate a number of important pathophysiological conditions in humans, like feeding, obesity, immune response, reproductive events, motor coordination, and neurological disorders. Hence, direct manipulation of the endocannabinoid tone is thought to have therapeutic potential. A new opportunity to develop effective drugs may arise from multi-target directed ligand (MTDL) strategies, which brings the concept that a single compound can recognize different targets involved in the cascade of pathophysiological events.

Areas covered: This review reports the latest advances in the development of new single targeted and dual-targeted FAAH inhibitors over the past 5 years.

Expert opinion: In recent years, several FAAH inhibitors have been synthesized and investigated, yet to date none of them has reached the market as a systemic drug. Due to the diligence of inherent redundancy and robustness in many biological networks and pathways, multitarget inhibitors present a new prospect in the pharmaceutical industry for treatment of complex diseases.

Keywords: Anandamide; FAAH; dual targets; inhibitors; single target.