192 W.-S.V. Ho and C.J. Hillard
Table 1.Inhibitors of FAAH activityInhibitor TissueIC
50(nM)ReferenceRemarksPMSFRat brain homogenates290Deutsch et al. 1997bIrreversible. Unstable in aqueous solution(t1/2<60 min, pH 7)Rat forebrain membranes13,000Hillard et al. 1995Solubilized from porcine brain∼
15,000Ueda et al. 1995AM374Rat brain homogenates13Deutsch et al. 1997bIrreversible; binds to CBreceptors (IC 150520 nM;Deutsch et al. 1997b)Brain microsomes50Lang et al. 1996ATFMKN18TG2 cells700Deutsch et al. 1997aReversible; inhibits cPLA(IC 2502–15 μM; Street et al. 1993);binds to CBreceptor (IC 1500.65–2.5 μM, Koutek et al. 1994)Rat brain homogenate900Deutsch et al. 1997bSolubilized porcine brain FAAH1,000Ueda et al. 1995Mouse neuroblastoma N18TG2 cells3,000Maurelli et al. 1995Rat brain microsomes4,000Beltramo et al. 1997aMAFPSolubilized from N18TG2 cells, RBL-1 cells,1–3De Petrocellis et al. 1997 Irreversible. Also inhibits cPLA(Lio et al. 1996). 2and porcine brain RBL-1 cells,Binds irreversibly to CBreceptor IC 15020 nM; Deutsch et al. 1997aand porcine brainRat brain homogenates2.5Deutsch et al. 1997aN18TG2 cells20Deutsch et al. 1997aDAKRat brain membranes500Edgemond et al. 1998Irreversible; binds to CBreceptors (IC 1501.3 μM;Edgemond et al. 1998)Solubilized from N18TG2 cells,2,000–6,000 De Petrocellis et al. 1997 ReversibleRBL-1 cells, and porcine brainAA-5-HT RBL-2H3 cells560Bisogno et al. 1998Reversible; inactive at cPLA,CB 2,orCB 1receptors 2N18TG2 cells1,200Bisogno et al. 1998URB597 Rat cortical neurons0.5Kathuria et al. 2003Irreversible; active in vivo at 0.3 mg/kgRat brain membranes4.6Kathuria et al. 2003AA-5-HT, arachidonoylserotonin; AM374, palmitylsulfonylfluoride; ATFMK, arachidonyltrifluoromethylketone; DAK, diazomethylarachidonylketone; MAFP, methylarachidonylflu-orophosphonate; PMSF, phenylmethylsulfonyl fluoride.