Table 5.
Effective Permeability (Pe) of Five Commercial Drugs and nNOS Inhibitors in the PAMPA–BBB Assaya
| Compd | log Db | log Pb | TPSA (Å2)c | reported Pe (10−6 cm s−1)d | determined Pe (10−6 cm s−1)e | BBB permeant predictionc | prediction |
|---|---|---|---|---|---|---|---|
| verapamil | 2.29 | 4.55 | 63.95 | 16 | 21.3 ± 1.5f 18.5 ± 1.9 | BBB (+) | CNS (+) |
| chlorpromazine | 2.76 | 4.56 | 31.78 | 6.5 | 8.04 ± 0.41f 8.90 ± 0.68 | BBB (+) | CNS (+) |
| dopamine | −1.50 | 0.03 | 66.48 | 0.2 | 0.12 ± 0.41f 0.125 ± 0.14 | BBB (−) | CNS (−) |
| 7 | 1.36 | 3.32 | 64.93 | 11.3 ± 1.64 | BBB (+) | CNS (+) | |
| 12 | 1.27 | 3.18 | 64.93 | 15.5 ± 2.32 | BBB (+) | CNS (+) | |
| 29 | 2.37 | 3.78 | 74.16 | 14.6 ± 0.97 | BBB (+) | CNS (+) | |
| 33 | 2.13 | 3.53 | 87.05 | 8.09 ± 0.67 | BBB (−) | CNS (+) | |
| 37 | 1.94 | 3.35 | 115.29 | 7.04 ± 2.43 | BBB (−) | CNS (+) |
a
All assays were performed over 17 h at a concentration of 200 μM; see Experimental Section for details.
b
Log D (pH = 7.4) and log P values of the free-base species were predicted using ChemAxon software.
c
TPSA calculations and BBB permeation was predicted using the free web tool SwissADME.
d
Effective permeability values from literature.32
e
Effective permeability values obtained in-house.
f
Experimental Pe values reported previously by Do et al.68