Table 3.
PDE inhibition and selectivity
| Drug | Geometric mean IC50 values (μM) [fold selectivity versus PDE5 in parentheses] | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PDE1 | PDE2 | PDE3 | PDE4 | PDE5 | PDE6 (rod) | PDE6 (cone) | PDE7A | PDE8A | PDE9A | PDE10A | PDE11A | |
| Sildenafil | 0.281 [80] | >30 [>8,570] | 16.2 [4,630] | 7.68 [2,190] | 0.00350 | 0.037 [11] | 0.034 [10] | 21.3 [6,090] | 29.8 [8,510] | 2.61 [750] | 9.80 [2,800] | 2.73 [780] |
| Tadalafil | >30 [>4,450] | >100 [>14,800] | >100 [>14,800] | >100 [>14,800] | 0.00674 | 1.26 [187] | 1.30 [193] | >100 [>14,800] | >100 [>14,800] | >100 [>14,800] | >100 [>14,800] | 0.037 [5] |
| Vardenafil | 0.070 [500] | 6.20 [44,290] | >1.0 [>7,140] | 6.10 [43,570] | 0.00014 | 0.0035 [25] | 0.0006 [4] | >30 [>214,000] | >30 [>214,000] | 0.581 [4,150] | 3.0 [21,200] | 0.162 [1,160] |
| IC50 values were determined using either native enzyme purified from human tissue (PDE1, heart; PDEs 2, 3 and 5, corpus cavernosum; PDE4, skeletal muscle; PDE6, retina) or using recombinant human enzymes expressed in Sf9 cells (PDEs 7?11) and purified by anion-exchange chromatography. Adapted from Ref. 29. IC50, drug concentration necessary to inhibit 50% of enzyme activity; PDE, phosphodiesterase. | ||||||||||||