CNS Drug | In Vitro P-gp Efflux Ratio | Kp,uu | Kp,uu | Kp,uu | |||
---|---|---|---|---|---|---|---|
Rat | mdr1a/b(+/+) Mouse | mdr1a/b(−/−) Mouse | |||||
Mean | S.D. | Mean | S.D. | Mean | S.D. | ||
Atenolol | — | 0.012 | 0.003 | — | — | — | — |
Amantadine | 0.8 | 3.01 | 0.85 | — | — | — | — |
Amitriptyline | 1.9 | 1.33 | 0.40 | — | — | — | — |
Amoxapine | 4.1 | 0.35 | 0.17 | 0.23 | 0.06 | 0.55 | 0.10 |
Atomoxetine | 3.4 | 2.13 | 0.85 | 2.35 | 0.17 | 4.10 | 0.35 |
Bupropion | 1.4 | 4.97 | 0.91 | 6.14 | 2.54 | 5.41 | 0.52 |
Carbamazepine | 0.8 | 0.76 | 0.20 | — | — | — | — |
Chlorpromazine | 0.8 | 3.41 | 0.81 | 2.79 | 0.42 | 3.19 | 0.45 |
Citalopram | 20.1 | 1.30 | 0.33 | 1.47 | 0.17 | 4.58 | 0.48 |
Clozapine | 1.3 | 3.83 | 0.80 | 2.51 | 0.14 | 2.84 | 0.32 |
Diazepam | 1.0 | 0.96 | 0.16 | — | — | — | — |
Donepezil | 2.3 | 1.77 | 0.23 | 1.19 | 0.09 | 2.64 | 0.29 |
Doxepin | 1.9 | 3.11 | 0.59 | — | — | — | — |
Ergotamine | 49.6 | 0.02 | 0.01 | <0.01 | — | 0.30 | 0.12 |
Ethosuximide | 0.8 | 1.50 | 0.75 | — | — | — | — |
Fluoxetine | 1.2 | 5.23 | 1.87 | — | — | — | — |
Fluphenazine | 2.3 | 1.58 | 0.57 | 6.12 | 1.31 | 7.77 | 1.25 |
Gabapentin | 0.8 | 0.44 | 0.11 | — | — | — | — |
Haloperidol | 1.3 | 1.77 | 0.71 | 1.54 | 0.21 | 1.89 | 0.49 |
Imipraminea | — | 3.52 | 0.32 | — | — | — | — |
Isocarboxazid | 1.2 | 0.18 | 0.04 | — | — | — | — |
Lamotrigine | 1.6 | 4.86 | 0.72 | 1.00 | 0.11 | 1.09 | 0.08 |
Loxapine | 1.2 | 2.95 | 0.89 | — | — | — | — |
Maprotiline | 4.0 | 0.98 | 0.47 | 1.42 | 0.44 | 3.06 | 0.45 |
Meprobamate | 3.3 | 0.77 | 0.10 | 0.61 | 0.10 | 0.80 | 0.20 |
Memantinea | — | 6.21 | 1.56 | — | — | — | — |
Mesoridazine | 87.1 | 0.10 | 0.03 | 0.19 | 0.02 | 3.30 | 0.73 |
Metoclopramide | 13.2 | 0.40 | 0.08 | 0.90 | 0.15 | 6.23 | 0.83 |
Mianserina | — | 3.22 | 0.43 | — | — | — | — |
Midazolam | 2.0 | 1.08 | 0.10 | — | — | — | — |
Mirtazapine | 1.3 | 3.85 | 0.50 | — | — | — | — |
Olanzapine | 4.9 | 2.13 | 0.60 | 6.86 | 1.52 | 9.53 | 1.38 |
Pemoline | 1.2 | 0.55 | 0.15 | — | — | — | — |
Pergolide | 1.8 | 3.19 | 0.59 | — | — | — | — |
Perphenazine | 4.7 | 7.12 | 2.17 | 5.99 | 1.53 | 6.17 | 1.58 |
Phenelzine | 1.4 | 1.48 | 0.34 | — | — | — | — |
Phenytoin | 2.8 | 0.66 | 0.11 | 3.05 | 0.42 | 2.79 | 0.37 |
Primidone | 3.6 | 0.38 | 0.10 | 0.68 | 0.10 | 1.25 | 0.22 |
Quetiapine | 1.5 | 1.26 | 0.14 | 1.15 | 0.20 | 1.27 | 0.34 |
Risperidone | 20.8 | 0.21 | 0.04 | 0.18 | 0.07 | 2.29 | 0.42 |
Rizatriptan | 8.4 | 0.04 | 0.01 | 0.40 | 0.27 | 0.53 | 0.10 |
Selegiline | 0.8 | 1.08 | 0.17 | — | — | — | — |
Sertraline | 2.6 | 2.67 | 0.51 | 3.87 | 1.03 | 4.22 | 1.52 |
Sumatriptan | 2.9 | 0.04 | 0.01 | 0.02 | 0.01 | 0.08 | 0.02 |
Tacrine | 1.1 | 1.61 | 0.56 | 2.25 | 0.83 | 2.68 | 0.97 |
Temazepam | 1.6 | 0.80 | 0.12 | — | — | — | — |
Thioridazine | 33.7 | 3.50 | 1.67 | — | — | — | — |
Thiothixene | 47.7 | 0.13 | 0.04 | 0.34 | 0.06 | 3.67 | 0.47 |
Tiagabine | 25.8 | 0.62 | 0.21 | 0.77 | 0.14 | 1.17 | 0.20 |
Trazodone | 1.1 | 1.54 | 0.28 | — | — | — | — |
Trifluoperazine | 7.3 | 3.35 | 1.10 | 2.18 | 0.47 | 3.35 | 0.70 |
Venlafaxine | 4.7 | 1.91 | 0.30 | 3.49 | 0.71 | 5.43 | 0.98 |
Zaleplon | 5.6 | 0.59 | 0.10 | 0.77 | 0.13 | 1.38 | 0.23 |
Ziprasidone | 1.7 | 0.75 | 0.22 | 4.10 | 0.91 | 7.17 | 1.85 |
Digoxin | — | — | — | 0.12 | 0.03 | 3.41 | 0.42 |
—, not determined.
↵a Kp values derived from oral dosing studies.