192 W.-S.V. Ho and C.J. Hillard
Table 1.
Inhibitors of FAAH activity
Inhibitor Tissue
IC
50
(nM)
Reference
Remarks
PMSF
Rat brain homogenates
290
Deutsch et al. 1997b
Irreversible. Unstable in aqueous solution
(t1/2
<60 min, pH 7)
Rat forebrain membranes
13,000
Hillard et al. 1995
Solubilized from porcine brain
∼
15,000
Ueda et al. 1995
AM374
Rat brain homogenates
13
Deutsch et al. 1997b
Irreversible; binds to CB
receptors (IC 1
50
520 nM;
Deutsch et al. 1997b)
Brain microsomes
50
Lang et al. 1996
ATFMK
N18TG2 cells
700
Deutsch et al. 1997a
Reversible; inhibits cPLA
(IC 2
50
2–15 μM; Street et al. 1993);
binds to CB
receptor (IC 1
50
0.65–2.5 μM, Koutek et al. 1994)
Rat brain homogenate
900
Deutsch et al. 1997b
Solubilized porcine brain FAAH
1,000
Ueda et al. 1995
Mouse neuroblastoma N18TG2 cells
3,000
Maurelli et al. 1995
Rat brain microsomes
4,000
Beltramo et al. 1997a
MAFP
Solubilized from N18TG2 cells, RBL-1 cells,
1–3
De Petrocellis et al. 1997 Irreversible. Also inhibits cPLA
(Lio et al. 1996). 2
and porcine brain RBL-1 cells,
Binds irreversibly to CB
receptor IC 1
50
20 nM; Deutsch et al. 1997a
and porcine brainRat brain homogenates
2.5
Deutsch et al. 1997a
N18TG2 cells
20
Deutsch et al. 1997a
DAK
Rat brain membranes
500
Edgemond et al. 1998
Irreversible; binds to CB
receptors (IC 1
50
1.3 μM;
Edgemond et al. 1998)
Solubilized from N18TG2 cells,
2,000–6,000 De Petrocellis et al. 1997 Reversible
RBL-1 cells, and porcine brain
AA-5-HT RBL-2H3 cells
560
Bisogno et al. 1998
Reversible; inactive at cPLA
,CB 2
,orCB 1
receptors 2
N18TG2 cells
1,200
Bisogno et al. 1998
URB597 Rat cortical neurons
0.5
Kathuria et al. 2003
Irreversible; active in vivo at 0.3 mg/kg
Rat brain membranes
4.6
Kathuria et al. 2003
AA-5-HT, arachidonoylserotonin; AM374, palmitylsulfonylfluoride; ATFMK, arachidon
yltrifluoromethylketone; DAK, diazomethylarachidonylk
etone; MAFP, methylarachidon
ylflu-
orophosphonate; PMSF, phenylmethylsulfonyl fluoride.