List of proprietary CNS compounds and marketed drugs with their physicochemical properties and fraction unbound [fu,brain (%)] in rat brain tissue homogenate (equilibrium dialysis) and TRANSIL assay
Acid/base was determined by ACD/PhysChem Suite, version 11. fu,brain (%) tissue homogenate (n = 3) and fu,brain (%) TRANSIL (n = 6) are shown as means with S.D. and CV%. Fold difference is the degree by which fu,brain (%) by equilibrium dialysis is overestimated or underestimated (in parentheses), with respect to data obtained using TRANSIL.
| Drug Name | Molecular Mass | HBA/HDB | Acid/Base | cLogP | PSA | fu,brain (%) ± S.D. Tissue Homogenate | CV% | fu,brain (%) ± S.D. TRANSIL | CV% | Fold Change |
|---|---|---|---|---|---|---|---|---|---|---|
| GSK28 | 392.6 | 0/2 | Base | 4.1 | 24.1 | 0.05 ± 0.01 | 20 | 0.05 ± 0.01 | 20 | 1 |
| Trifluoperazine | 407.5 | 0/0 | Base | 4.6 | 9.7 | 0.070 ± 0.01 | 14 | 0.180 ± 0.005 | 6 | (2.6) |
| Thioridazine | 370.6 | 0/0 | Base | 5.9 | 6.5 | 0.10 ± 0.01 | 10 | 0.030 ± 0.001 | 3 | 3.3 |
| GSK27 | 424.5 | 1/2 | Neutral | 4.9 | 70.3 | 0.10 ± 0.02 | 20 | 0.17 ± 0.01 | 3 | (1.7) |
| GSK32 | 491.5 | 1/1 | Base | 5.7 | 35.6 | 0.11 ± 0.01 | 9 | 0.06 ± 0.01 | 17 | 1.8 |
| GSK38 | 445.5 | 3/0 | Neutral | 3.4 | 65.3 | 0.13 ± 0.01 | 8 | 0.30 ± 0.01 | 3 | (2.3) |
| GSK30 | 624.7 | 3/2 | Base | 2.1 | 88.3 | 0.14 ± 0.01 | 7 | 0.20 ± 0.01 | 5 | (1.4) |
| GSK33 | 588.6 | 2/2 | Base | 5.7 | 78.7 | 0.18 ± 0.01 | 6 | 0.20 ± 0.01 | 5 | (1.1) |
| Chlorpromazine | 318.9 | 0/0 | Base | 5.2 | 6.5 | 0.20 (S) | 0.22 ± 0.01 | 5 | (1.1) | |
| Paroxetine | 329.4 | 0/1 | Base | 3.7 | 39.7 | 0.39 (M) | 0.26 ± 0.01 | 4 | 1.5 | |
| GSK34 | 380.4 | 1/2 | Base | 3.9 | 73.6 | 0.44 ± 0.05 | 11 | 0.27 ± 0.01 | 4 | 1.6 |
| Fluoxetine | 309.4 | 0/1 | Base | 3.9 | 21.3 | 0.4 ± 0.1 | 25 | 0.30 ± 0.01 | 3 | 1.3 |
| GSK31 | 616.7 | 2/0 | Neutral | 5.6 | 47.1 | 0.40 ± 0.05 | 13 | 0.36 ± 0.01 | 3 | 1.1 |
| Nortriptyline | 263.4 | 0/1 | Base | 4 | 12 | 0.46 (M) | 0.40 ± 0.01 | 3 | 1.2 | |
| GSK10 | 458.5 | 2/2 | Base | 2.5 | 57.3 | 0.72 ± 0.06 | 8 | 0.42 ± 0.01 | 2 | 1.7 |
| Cyclobenzaprine | 275.4 | 0/0 | Base | 6.2 | 3.2 | 0.73 (M) | 1.0 ± 0.1 | 10 | (1.4) | |
| Fluvoxamine | 318.4 | 3/1 | Base | 3.7 | 56.8 | 0.84 (M) | 0.74 ± 0.05 | 7 | 1.1 | |
| Amitriptylline | 277.4 | 0/0 | Base | 4.4 | 3.2 | 0.9 ± 0.1 | 11 | 0.73 ± 0.01 | 1 | 1.2 |
| GSK1 | 327.4 | 3/2 | Neutral | 2.3 | 67 | 1.0 | 0.33 ± 0.01 | 3 | 3 | |
| GSK15 | 378.5 | 3/2 | Neutral | 1.9 | 74 | 1.0 | 0.70 ± 0.05 | 7 | 1.4 | |
| GSK26 | 378.5 | 3/2 | Neutral | 1.9 | 74 | 1.0 | 0.70 ± 0.03 | 4 | 1.4 | |
| Hydroxyzine | 375 | 2/1 | Base | 2.3 | 35.9 | 1.02 (M) | 2.1 ± 0.1 | 5 | (2.1) | |
| Clozapine | 326.9 | 0/1 | Neutral | 3.9 | 30.9 | 1.1 ± 0.1 | 9 | 0.72 ± 0.02 | 3 | 1.5 |
| Haloperidol | 375.9 | 2/1 | Base | 3.8 | 40.5 | 1.1 ± 0.1 | 9 | 1.4 ± 0.1 | 7 | (1.3) |
| GSK2 | 370.4 | 3/2 | Neutral | 5.7 | 75.5 | 1.2 ± 0.1 | 8 | 0.81 ± 0.01 | 1 | 1.5 |
| GSK7 | 355.9 | 3/1 | Neutral | 3 | 66.1 | 1.8 ± 0.1 | 6 | 1.1 ± 0.1 | 9 | 1.6 |
| GSK18 | 448.5 | 2/1 | Neutral | 3.5 | 67.4 | 1.8 ± 0.2 | 11 | 2.3 ± 0.1 | 4 | (1.3) |
| GSK12 | 382.8 | 3/1 | Neutral | 2.8 | 81.7 | 2.2 ± 0.4 | 18 | 1.0 ± 0.1 | 10 | 2.2 |
| GSK24 | 484.6 | 3/0 | Base | 3.4 | 69.4 | 2.3 ± 0.1 | 4 | 2.0 ± 0.1 | 5 | 1.2 |
| Midazolam | 325.8 | 2/0 | Neutral | 3.8 | 30.2 | 2.3 ± 0.1 | 4 | 4.1 ± 0.2 | 5 | (1.8) |
| GSK11 | 357.8 | 3/1 | Neutral | 2.5 | 77.3 | 3.0 ± 0.5 | 17 | 1.7 ± 0.1 | 6 | 1.8 |
| Propranolol | 259.4 | 1/2 | Base | 2.9 | 41.5 | 3.0 ± 0.3 | 10 | 2.0 ± 0.1 | 5 | 1.5 |
| GSK25 | 363.5 | 4/1 | Neutral | 3.2 | 76.7 | 3.2 ± 0.6 | 19 | 4.2 ± 0.2 | 5 | (1.3) |
| Diazepam | 284.8 | 2/0 | Neutral | 2.8 | 32.7 | 3.6 ± 0.5 | 14 | 8.3 ± 0.4 | 5 | (2.3) |
| GSK22 | 302.4 | 1/2 | Neutral | 2.1 | 64.4 | 3.7 ± 0.4 | 11 | 2.0 ± 0.1 | 5 | 1.9 |
| GW17 | 375.6 | 2/0 | Zwitterion | 4 | 40.5 | 7.3 ± 1 | 14 | 6.0 ± 0.4 | 7 | (1.2) |
| GSK21 | 581.7 | 5/4 | Neutral | 1 | 126.2 | 5.1 ± 0.8 | 16 | 7.0 ± 0.3 | 4 | (1.4) |
| GSK3 | 356.4 | 5/1 | Acid | 0.9 | 93.7 | 5.5 ± 0.2 | 4 | 3.7 ± 0.2 | 5 | 1.5 |
| Trazodone | 371.9 | 2/0 | Base | 2.8 | 45.8 | 5.5 ± 0.6 | 11 | 5.7 ± 0.6 | 11 | 1 |
| GSK35 | 321.4 | 2/2 | Base | 2.9 | 88.1 | 6.8 ± 0.5 | 7 | 5.1 ± 0.1 | 2 | 1.3 |
| GSK19 | 309.5 | 1/0 | Base | 2.2 | 20.3 | 6.3 ± 0.8 | 13 | 4.2 ± 0.1 | 2 | 1.5 |
| GSK29 | 402.4 | 2/0 | n/c | 4.8 | 37.6 | 7.4 ± 0.6 | 8 | 6.2 ± 0.2 | 3 | 1.2 |
| GSK14 | 437.6 | 3/2 | Base | 3.2 | 81.3 | 7.5 ± 0.2 | 3 | 5.8 ± 0.4 | 7 | 1.3 |
| Phenytoin | 252.3 | 2/2 | Neutral | 1.4 | 58.2 | 8.1 ± 0.6 | 7 | 4.7 ± 0.2 | 4 | 1.7 |
| GSK36 | 448.6 | 3/0 | n/c | 4.8 | 50.5 | 9.0 ± 1 | 11 | 12.2 ± 0.2 | 2 | (1.4) |
| Risperidone | 410.5 | 3/0 | Base | 2.7 | 64.2 | 9.9 ± 0.3 | 3 | 5.7 ± 0.6 | 11 | 1.7 |
| GSK16 | 466 | 4/0 | Neutral | 2.4 | 63.4 | 10.5 ± 0.6 | 6 | 9.8 ± 0.7 | 7 | 1.1 |
| GSK13 | 362.5 | 4/3 | Neutral | 1 | 96.1 | 12 ± 2 | 17 | 16 ± 2 | 13 | (1.3) |
| GSK8 | 377.5 | 3/1 | Neutral | 2 | 66.1 | 11.9 ± 0.1 | 1 | 10.2 ± 0.5 | 5 | 1.2 |
| Carbamazepine | 236.3 | 1/1 | Neutral | 1.9 | 46.3 | 11.9 ± 0.7 | 6 | 13.2 ± 0.9 | 7 | (1.1) |
| GSK23 | 434.6 | 3/0 | n/c | 3.2 | 50.5 | 14.1 ± 2 | 14 | 17.3 ± 0.7 | 4 | (1.2) |
| Buproprion | 239.8 | 1/1 | Neutral | 2.3 | 29.1 | 17 ± 3 | 18 | 17 ± 4 | 24 | 1 |
| Carisoprodol | 260.4 | 2/2 | Neutral | 2.1 | 90.7 | 20.2 (M) | 29.5 ± 2 | 7 | (1.5) | |
| Venlafaxine | 277.5 | 1/1 | Base | 2.5 | 32.7 | 21 ± 2.2 | 10 | 12.3 ± 1 | 8 | 1.7 |
| Buspirone | 385.6 | 4/0 | Neutral | 1.6 | 69.6 | 22 (M) | 24.0 ± 1 | 4 | (1.1) | |
| GSK37 | 416.6 | 3/0 | n/c | 3.7 | 50.5 | 23 ± 3 | 13 | 38 ± 3 | 8 | (1.7) |
| Bupivacaine | 288.5 | 1/1 | Base | 3.3 | 32.3 | 27.8 ± 3 | 11 | 17 ± 3 | 18 | 1.6 |
| GSK5 | 385.5 | 5/3 | Neutral | 0 | 109 | 31.7 ± 0.9 | 3 | 47 ± 4 | 9 | (1.5) |
| GSK9 | 310.3 | 4/1 | Neutral | 1 | 90.1 | 33 ± 5 | 15 | 9.8 ± 0.5 | 5 | 3.3 |
| GSK6 | 385.5 | 5/3 | Neutral | 0 | 109 | 34 ± 3 | 9 | 39 ± 10 | 26 | (1.1) |
| GSK4 | 399.5 | 5/3 | Neutral | −0.2 | 109 | 36 ± 6 | 17 | 21 ± 4 | 19 | 1.7 |
| Metoclopramide | 299.8 | 1/2 | Base | 2.2 | 67.6 | 36 ± 5 | 14 | 29.5 ± 4 | 14 | 1.2 |
| GSK20 | 384.5 | 3/0 | Zwitterion | 3 | 61.6 | 45 ± 6 | 13 | 24.2 ± 0.4 | 2 | 1.9 |
| Caffeine | 194.2 | 3/0 | Neutral | −0.6 | 61.8 | 52 (M) | 26 ± 2 | 8 | 2 | |
| Sulpiride | 341.5 | 3/2 | Base | 0.8 | 101.7 | 63 (M) | 24 ± 2 | 8 | 2.6 |
n/c, not calculated; (M), Maurer et al. (2005); (S), Summerfield et al. (2007).