Table 2.
Compound | Rat brain FAAH (IC50, μM) | Rat brain FAAH (% inhibition at max concentration tested in μM, shown in parentheses) | Rat brain FAAH following pre-incubation (IC50, μM) | Rat brain FAAH following pre-incubation (% inhibition at max concentration tested in μM, shown in parentheses) | Mouse N18TG2 cell FAAH (IC50, μM) | Human recombinant FAAH (% inhibition at 10 μM) |
---|---|---|---|---|---|---|
AGN 205492 | 8.3 ± 0.4 | 63.8 (10) | ND | ND | 9.7 ± 0.6 | ND |
AGN 205493 | 4.8 ± 0.3 | 72.5 (10) | ND | ND | 8.7 ± 0.5 | ND |
AGN 205494 | 3.7 ± 0.2 | 75.9 (10) | ND | ND | 5.9 ± 0.5 | ND |
AGN 204396 | 22.2 ± 0.8 | 51.7 (25) | 3.9 ± 0.1 | 84.9 (10) | 13.4 ± 0.7 | ND |
AGN 204397 | 12.8 ± 0.5 | 73.1 (25) | 6.6 ± 0.4 | 67.9 (10) | 8.5 ± 0.4 | ND |
AGN 211334 | 7.5 ± 0.4 | 73.9 (10) | ND | ND | ND | ND |
AGN 211335 | 3.0 ± 0.05 | 76.8 (5) | 1.2 ± 0.3 | 96.9 (5) | 3.4 ± 0.3 | 48.5 |
AGN 211336 | 3.6 ± 1.1 | 71.9 (5) | 1.3 ± 0.3 | 97.8 (5) | 3.1 ± 0.2 | 24.8 |
URB597 | – | – | 0.01 ± 0.003 | 98.1 (0.1) | – | 0.1 ± 0.02 |
Data are expressed as means ± SD of two separate experiments conducted in duplicate of the concentrations exerting 50% inhibition of [14C]-AEA hydrolysis (IC50) calculated by fitting sigmoidal concentration–response curves by GraphPad. For some experiments, the average effect observed with the maximal tested concentration (indicated between parentheses) was also shown (without SD for the sake of clarity). ND, not determined.