TABLE 1

Transwell assays using MDR1-MDCK, Mdr1a-MDCK, and MDCK cells, ATPase assay, calcein AM P-gp inhibition assay, and brain/plasma AUC ratios in MDr1a/1b (-/-, -/-) and FVB mice for 32 CNS-active compounds

Boldface indicates positive efflux.


Drugs

B/P in KO/WTa

MDR1-MDCK Efflux Ratiob

Mdr1a-MDCK Efflux Ratiob

MDCK Efflux Ratiob

Ratio of Ratios in MDR1-MDCK/MDCK

Ratio of Ratios in Mdr1a-MDCK/MDCK

ATPase Kmb

Calcein IC50
μM μM
Buspirone 1.3 0.8 ± 0.11 0.6 ± 0.02 0.8 ± 0.14 1.0 0.8 118 ± 22.2 17.5
Caffeine 1.1 0.6 ± 0.07 0.6 ± 0.01 0.4 ± 0.29 1.4 1.5 Neg >100
Carbamazepine 1.1 0.7 ± 0.06 0.7 ± 0.06 0.8 ± 0.10 0.9 0.9 Neg >100
Carisoprodol 1.2 0.7 ± 0.03 0.7 ± 0.07 0.9 ± 0.15 0.8 0.8 Neg >100
Chlorpromazine 1.3 1.5 ± 0.49 1.8 ± 0.75 2.9 ± 1.34 0.5 0.6 41.0 ± 1.07 15.2
Citalopram 1.9 1.3 ± 0.27 1.0 ± 0.05 0.8 ± 0.19 1.6 1.2 441 ± 140.1 52.5
Cyclobenzaprine 1.4 0.5 ± 0.05 0.5 ± 0.02 0.6 ± 0.06 1.0 0.9 77.4 ± 26.86 18.7
Diazepam 1.2 0.7 ± 0.08 0.7 ± 0.05 0.9 ± 0.14 0.8 0.8 141 ± 38.0 100.5
Ethosuximide 1.0 0.8 ± 0.07 0.8 ± 0.03 0.9 ± 0.03 0.9 0.9 Neg >100
Fluoxetine 1.5 0.6 ± 0.06 0.7 ± 0.07 1.2 ± 0.12 0.5 0.6 51.6 ± 11.81 31.0
Fluvoxamine 2.3 0.7 ± 0.17 0.6 ± 0.12 0.8 ± 0.31 0.9 0.8 180 ± 35.7 >100
Haloperidol 1.4 0.8 ± 0.28 0.7 ± 0.25 1.0 ± 0.47 0.8 0.7 Neg 7.2
Hydrocodone 2.1 0.9 ± 0.10 0.9 ± 0.05 0.8 ± 0.05 1.1 1.0 Neg >100
Hydroxyzine 1.0 0.6 ± 0.09 0.5 ± 0.09 0.8 ± 0.28 0.8 0.7 100 ± 42.7 19.1
Lamotrigine 1.0 0.7 ± 0.04 0.7 ± 0.03 0.8 ± 0.01 0.9 0.9 Neg >100
Methylphenidate 1.6 0.8 ± 0.06 0.8 ± 0.07 0.9 ± 0.10 0.9 0.9 Neg >100
Metoclopramide 6.6* 1.1 ± 0.27 1.1 ± 0.18 0.8 ± 0.18 1.4 1.4 Neg >100
Midazolam 1.0 0.7 ± 0.06 0.7 ± 0.08 0.8 ± 0.15 0.9 0.8 44.4 ± 5.06 >100
Morphine 1.7 1.7 ± 0.23 1.7 ± 0.31 1.4 ± 0.28 1.3 1.3 Neg >100
Nortriptyline 1.8 0.6 ± 0.03 0.5 ± 0.05 0.6 ± 0.03 1.1 0.9 56.0 ± 15.73 >100
Paroxetine 2.2 0.7 ± 0.02 0.7 ± 0.07 0.7 ± 0.01 1.0 1.0 26.2 ± 1.02 27.5
Phenytoin 1.2 0.9 ± 0.09 0.8 ± 0.03 0.9 ± 0.08 1.0 0.9 Neg >100
Propoxyphene 2.6 0.7 ± 0.14 0.6 ± 0.07 0.7 ± 0.17 1.0 0.9 180 ± 67.5 63.3
Risperidone 10* 1.2 ± 0.36 1.1 ± 0.19 0.6 ± 0.30 2.0 1.8 36.1 ± 1.23 70.7
9-Hydroxyrisperidone 17* 2.1 ± 0.18 3.0 ± 0.20 0.6 ± 0.31 3.3 4.7 177 ± 1.2 >100
Selegiline 1.1 0.8 ± 0.08 0.8 ± 0.04 0.9 ± 0.14 0.8 0.8 Neg >100
Sertraline 1.1 3.6 ± 0.42 5.4 ± 0.56 10.0 ± 1.09 0.4 0.5 9.4 ± 1.45 30.0
Sulpiride 1.9 0.9 ± 0.59 2.7 ± 1.62 2.0 ± 0.74 0.5 1.4 Neg >100
Thiopental 1.2 0.9 ± 0.07 0.8 ± 0.03 0.9 ± 0.08 1.0 0.9 Neg >100
Trazodone 0.9 0.8 ± 0.03 0.7 ± 0.07 0.8 ± 0.11 0.9 0.9 172 ± 44.5 >100
Venlafaxine 1.8 0.6 ± 0.02 0.7 ± 0.03 0.7 ± 0.01 0.9 1.0 Neg >100
Zolpidem
1.4
0.7 ± 0.06
0.6 ± 0.04
0.7 ± 0.06
1.0
0.9
198 ± 1.0
>100
  • Neg, no stimulation of ATPase activity.

  • * P < 0.05, probability of KO/WT ratio > 4.

  • a The data for B/P in P-gp KO/WT mice were extracted from Doran et al. (2005).

  • b Data are presented as mean ± S.D.