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PF-3845 is a highly potent and selective inhibitor of fatty acid amide hydrolase (FAAH) with Ki value of 0.23μM [1].

PF-3845 is a biaryl ether piperidine. It inhibits FAAH by a covalent, irreversible mechanism involving carbamylating FAAH's catalytic S241 nucleophile. It is found that, administration of PF-3845 to mice results a rapid and complete inactivation of FAAH in the brain. PF-3845 is highly selective for FAAH in vivo. It shows no activity to some other serine hydrolases as well as to a FAAH homologue, FAAH2. In addition, PF-3845-treated mice shows significant elevations in brain levels of AEA, other NAEs and liver levels of AEA, PEA and OEA. Moreover, PF-3845 is found to inhibit pain responses in a rat model of inflammatory pain. It is also found to reverse LPS-induced tactile allodynia in mice. This anti-allodynic effect requires activation of both CB1 and CB2 receptors which are the target receptors of the FAAH substrates [

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