Interaction of the N-(3-Methylpyridin-2-yl)amide Derivatives of Flurbiprofen and Ibuprofen with FAAH: Enantiomeric Selectivity and Binding Mode
Fig 2
Time-dependency and reversibility of the inhibition of rat brain FAAH by (R)-Flu-AM1.
Panels A and B show the time-dependencies of (R)-Flu-AM1 and URB597, respectively. The data are means ± SEM, N = 3. In Panel C, homogenates (at 20-fold normal strength) were preincubated with either vehicle, 2, 4 or 6 μM (R)-Flu-AM1 for 60 min. Aliquots were then diluted 20-fold and assayed for FAAH activity. These are shown as 2 →0.1, 4 →0.2 and 6 →0.3. Concomitantly, (R)-Flu-AM1 was added to vehicle-preincubated aliquots to give concentrations of 0.1, 0.2 and 0.3 μM (representing free concentrations after a 20- fold dilution), 2, 4 and 6 μM final concentrations. The panel shows the data as % of corresponding control (means ± SEM, N = 3). For a fully reversible compound, the inhibition seen in the yellow bars (i.e. following the dilution) should be lower than in the purple bars (the inhibition seen at the undiluted concentrations) but equal to the green bars (the free concentrations after the dilution).
