PF-3845 is an orally-available, covalent and irreversible inhibitor of fatty acid amide hydrolase (FAAH) for the treatment of inflammation and pain, with an IC50 of 7.2 nM. [1] Mechanistic studies show that PF-3845 is a time-dependent inhibitor that carbamylates FAAH's catalytic serine nucleophile and raises anandamide levels in the brain for up to 24h. [2, 3]

Oral administration of PF-3845 produces antinociceptive effects in both inflammatory and noninflammatory pain models in rats with an MED 0.1 mg/kg. [2] Furthermore, oral administration of PF-3845 at 0.1 mg/kg results in efficacy comparable to that of naproxen at 10 mg/kg in a rat inflammatory pain model. [1]

Regarding the encannabinoid system, PF-3845 has been shown to be an effective treatment (i.p.) for the blockade of neuronal FAAH to reverse allodynia through the activation of both cannabinoid receptors, without the psychomimetic side effects associated with THC. [4]