title: Latest advances in the discovery of fatty acid amide hydrolase inhibitors.
abstract: BACKGROUND
  Fatty acid amide hydrolase (FAAH) is the major catabolic enzyme of the endocannabinoid N-arachidonoylethanolamine (anandamide) that, with different degrees of efficiency, also hydrolyzes other endogenous fatty acid ethanolamides. FAAH is increasingly being considered a relevant therapeutic target, especially in models of inflammatory pain. The opportunity to selectively increase the endocannabinoid tone only in those tissues where such an enhancement can be beneficial might result in a therapeutic benefit with more limited side effects, compared to the use of direct agonists of anandamide-binding receptors. Thus the research for selective FAAH inhibitors has become a hot topic in current drug discovery.
  
  
  METHODS
  This review highlights the advances in the development of different compounds belonging to different chemical families that have been proposed as FAAH inhibitors. Several classes of inhibitors have been reported so far, and they may be classified into two major classes: reversible and irreversible compounds. These inhibitors are reviewed herein with an emphasis on their potency and selectivity.
  
  
  CONCLUSIONS
  In recent years, tremendous efforts have been made to develop the FAAH inhibitors, and consequently many novel chemical templates have been discovered. It is still a major challenge to identify the first inhibitor of FAAH suitable for clinical exploitation that satisfies the requirements of potency, selectivity versus proteins related to anandamide activity as well as other potential off-targets, reversibility versus irreversibility, and efficacy toward rat versus human FAAH.
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry/Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bisogno
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D055808:Drug Discovery; D063388:Endocannabinoids / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D000099252:Fatty Acid Amide Hydrolases