PF-3845 is a potent, selective, and irreversible fatty acid amide hydrolase (FAAH) inhibitor with a Ki of 0.23 μM. Fatty acid amide hydrolase (FAAH) is an enzyme that catalyzes N-acyl ethanolamines (NAEs), including the endocannabinoid arachidonoyl ethanolamide (AEA). Mechanistic and structural studies demonstrated that PF-3845 acts as a covalent inhibitor and carbamylates the active site serine241 of FAAH. PF-3845 covalently binds FAAH on Ser241 at the catalytic site, resulting in prolonged elevation of AEA in the brain and plasma in rats after treatment. Initial experiments indicated that PF-3845 is 10 to 20 times more potent than other FAAH inhibitors and has superior pharmacokinetic properties. PF-3845 significantly and persistently blockes inflammatory pain in rats through a cannabinoid receptor-dependent mechanism. In animal studies, PF-3845 elevated brain anandamide levels for up to 24 hours and produced a marked cannabinoid receptor-dependent reduction in inflammatory pain.
||Male C57BL/6 mice
||PF-3845 is dissolved at 1 mg/ml by sonication and vortexing directly into a solution of 18:1:1 v/v/v saline:emulphor:ethanol.
||10 mg/kg or 1-30 mg/kg
||Administered via i.p. 1 hour before sacrificed by CO2 or oral administration.
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
|Body Surface Area (m2)
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by
||Animal B Km
|Animal A Km
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
||DMSO 90 mg/mL