Fatty acid amide hydrolase (FAAH) degrades N-acyl ethanolamines (NAEs), including the endocannabinoid arachidonoyl ethanolamide (AEA). PF-3845 is a potent, selective, and irreversible inhibitor of FAAH (Ki = 0.23 μM). It covalently binds FAAH on Ser241 at the catalytic site, resulting in prolonged elevation of AEA in the brain and plasma in rats after treatment. PF-3845 significantly and persistently reduces inflammatory pain in rats through a cannabinoid receptor-dependent mechanism.
