BIA 10-2474

BIA 10-2474 is an experimental fatty acid amide hydrolase inhibitor developed by the Portuguese pharmaceutical company Bial-Portela & Ca. SA. It interacts with the human endocannabinoid system. The drug was in development for the treatment of a range of different medical conditions from anxiety disorder to Parkinson's disease, also for the treatment of chronic pain of multiple sclerosis, cancer, hypertension or the treatment of obesity. A clinical trial with this drug was underway in Rennes, France, in January 2016, in which serious adverse events occurred affecting five participants, including the death of one man. The underlying mechanism that caused the acute neurotoxicity of this molecule remains unknown. The chemical name of BIA-10-2474 is 3-(1-(cyclohexyl(methyl)carbamoyl)-1H-imidazol-4-yl)pyridine 1-oxide. BIA-10-2474 is a long-acting inhibitor of fatty acid amide hydrolase (FAAH) that increases levels of the neurotransmitter anandamide in the central nervous system and in peripheral tissues (that is, the rest of the body other than the brain and spinal cord). In normal tissues, the enzyme FAAH degrades anandamide and other endocannabinoid neurotransmitters, which relieve pain and can affect eating and sleep patterns. FAAH inhibitors have been proposed for a range of nervous system disorders including anxiety disorders, alcoholism, pain and nausea. The Portuguese pharmaceutical company Bial holds several patents on FAAH enzyme inhibitors. The structure and synthesis of BIA 10-2474 is disclosed in a Bial patent as 'compound 362', part of a Bial patent family dating from December 2008. The patent discloses limited details about BIA 10–2474, mainly the screening assay results for each of the several hundred candidate compounds to evaluate the effect on FAAH activity. For compound 362 (that is, BIA 10–2474), an in vitro assay in rat brain showed only modest FAAH inhibition, however, mice given compound 362 at 3 mg/kg orally had less than 2% the normal level of FAAH activity in both brain and liver tissues after 8 hours.