TABLE 1

NSAID	In vitro actions	In vivo actions
Ibuprofen	pH-dependent inhibition of rat brain and recombinant FAAH (IC50 value 130  M at pH 6) (Holt et al., 2001; Holt et al., 2007); no inhibition of MGL (Holt et al., 2007); partial inhibition of [3H]CP55,940 binding to CB1 and CB2 receptors only at 300  M but not at 100  M (Holt et al., 2007)	Local administration to paw and formalin test of inflammatory pain in rats: no AM251-sensitive action per se, but AM251-sensitive synergy with AEA (Guindon et al., 2006a). Synergistic effect with AEA on paw AEA, PEA and OEA levels (Guindon et al., 2006b)
Indomethacin	pH-dependent inhibition of rat brain FAAH (IC50 value 17  M at pH 6) (Fowler et al., 2003); no inhibition of MGL (Holt et al., 2007). Inhibits [3H]CP55,940 binding to CB1 and CB2 at concentrations 100  M (Holt et al., 2007)	Intrathecally administered indomethacin is active in formalin test in mice in a manner blocked by AM251 (Gühring et al., 2002). This effect of indomethacin is not seen in CB-/- mice (Gühring et al., 2002). In contrast, the ability of oral indomethacin to attenuate visceral pain (p-phenylquinone stretch model) is not affected by either rimonabant or SR144528 (Anikwue et al., 2002)
Flurbiprofen	pH-dependent inhibition of rat brain FAAH (IC50 values 31 and 13  M for (R)- and (S)-enantiomers at pH 6) (Fowler et al., 2003); 3  M flurbiprofen decreases calcitonin gene-related peptide release from perfused rat spinal cord in a manner blocked by AM251 (Seidel et al., 2003)	Intrathecally administered flurbiprofen active in formalin test in rats in a manner blocked by AM251 (Ates et al., 2003)
Rofecoxib	No data, but the related compound celecoxib is a weak FAAH inhibitor (IC50 value 300  M, not pH-dependent) (Fowler et al., 2003)	Local administration to paw and formalin test in rats: synergistic effect with AEA on paw AEA, PEA and OEA levels (Guindon et al., 2006b)

 Abbreviations: AEA, anandamide; CB, cannabinoid; FAAH, fatty acid amide hydrolase; IC₅₀, half-maximal inhibitory concentration; MGL, monoacylglycerol lipase; NSAID, non-steroidal anti-inflammatory drug; OEA, oleoylethanolamide; PEA, palmitoylethanolamide.

 Indomethacin has also been reported to reduce carrageenan-induced oedema in pentobarbital-treated mice in a manner prevented by SR144528 (N-[(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylben-zyl)-pyrazole-3-carboxamide) (Holt et al., 2005). It is not, however, clear whether this reflects the ability of SR144528 to block CB₂ receptors (Rinaldi-Carmona et al., 1998) or to prevent effects mediated by PPAR (Lo Verme et al., 2006).