Although irreversible carbamate FAAH inhibitors (e.g., URB597; (Kathuria et al., 2003)) and inhibit FAAH and increase brain levels of anandamide in vivo, they also inhibit other serine hydrolases, calling into question their selectivity for FAAH (Lichtman et al., 2004). Reversible α-ketoheterocycle FAAH inhibitors (e.g. OL-92, OL-135; (Boger et al., 2005; Lichtman et al., 2004)) are more selective for FAAH than URB597, but cause milder elevations of anandamide in vivo. Recently, a new class of highly selective and potent piperidine urea FAAH inhibitors (e.g. PF-3845; (Ahn et al., 2009)) has been synthesized. PF-3845 has a 10-fold higher binding affinity for FAAH than URB597 (Ahn et al., 2009) and inhibits FAAH for at least 24 h in vivo. Similarly, although several compounds inhibit MAGL, these compounds have been criticized because they lack selectivity for MAGL. For example, URB602 lacks potency to systemically elevate 2-AG in vivo (King et al., 2007) and has similar selectivity for both MAGL and FAAH (Vandevoorde et al., 2007). However, JZL184 (Long et al., 2009) potently inhibits MAGL in vivo and is highly selective (200-fold higher for MAGL
