TABLE 4

B/P, CSF/plasma, and CSF/brain AUC ratios in FVB and mdr1a/1b (-/-, -/-) mice for 33 CNS-active agents


Compound

Brain/Plasma

CSF/Plasma

CSF/Brain
FVB
KO
KO/WT
FVB
KO
KO/WT
FVB
KO
KO/WT
Buspirone 1.6 2.0 1.3* 0.051 0.038 0.75 0.031 0.019 0.61
Caffeine 1.0 1.1 1.1* 0.079 0.12 1.5 0.082 0.10 1.2
Carbamazepine 0.76 0.81 1.1* 0.35 0.38 1.1 0.46 0.47 1.0
Carisoprodol 0.66 0.81 1.2 0.28 0.36 1.3* 0.43 0.45 1.0
Chlorpromazine 23 29 1.3* 0.025 0.012 0.48 0.0011 0.00043 0.39
Citalopram 5.1 9.7 1.9* 0.53 0.77 1.5* 0.10 0.079 0.79
Clozapine 4.1 6.6 1.6* 0.075 0.091 1.2* 0.018 0.014 0.78
Cyclobenzaprine 12 16 1.4* 0.057 0.091 1.6* 0.0049 0.0058 1.2
Diazepam 2.0 2.3 1.2* 0.066 0.059 0.89 0.034 0.025 0.74
Ethosuximide 1.1 1.1 1.0 1.6 1.6 1.0 1.4 1.5 1.1
Fluoxetine 12 18 1.5* 0.031 0.040 1.3* 0.0027 0.0022 0.81
Fluvoxamine 6.1 14 2.3** 0.058 0.093 1.6* 0.010 0.0068 0.72
Haloperidol 13 18 1.4* 0.14 0.18 1.3* 0.011 0.010 0.91
Hydrocodone 2.1 4.5 2.1* 0.56 1.0 1.8* 0.27 0.22 0.81
Hydroxyzine 7.7 7.6 1.0 0.073 0.067 0.92 0.0095 0.0089 0.94
Lamotrigine 1.1 1.1 1.0 0.15 0.13 0.87 0.14 0.13 0.93
Meprobamatea 0.42 0.70 1.7* 0.39 1.2 3.1* 0.93 1.8 1.9
Methylphenidate 12 19 1.6* 1.1 1.5 1.4* 0.090 0.078 0.87
Metoclopramide 1.2 7.9 6.6** 0.44 1.2 2.7** 0.36 0.15 0.42
Midazolam 0.23 0.24 1.0 0.056 0.081 1.4 0.25 0.33 1.3
Morphine 0.46 0.76 1.7* 0.64 0.78 1.2* 1.4 1.0 0.71
Nortriptyline 11 20 1.8* 0.024 0.036 1.5* 0.0021 0.0017 0.81
Paroxetine 3.3 7.1 2.2* 0.015 0.025 1.7* 0.0044 0.0035 0.80
Phenytoin 0.63 0.78 1.2* 0.18 0.18 1.0 0.28 0.24 0.86
Propoxyphene 2.9 7.6 2.6** 0.20 0.34 1.7* 0.070 0.046 0.66
Risperidone 0.78 8.0 10** 0.019 0.12 6.3** 0.025 0.015 0.60
9-OH-Risperidone 0.060 1.0 17** 0.045 0.42 9.3** 0.74 0.42 0.57
Selegiline 3.7 4.1 1.1* 0.44 0.42 1.0 0.12 0.10 0.83
Sertraline 24 27 1.1 N.D. N.D. N.D. N.D.
Sulpiride 0.078 0.15 1.9* 0.038 0.073 1.9 0.48 0.48 1.0
Thiopental 0.36 0.44 1.2* 0.046 0.065 1.4* 0.13 0.15 1.2*
Trazodone 0.61 0.54 0.89 0.037 0.043 1.2 0.061 0.079 1.3*
Venlafaxine 4.2 7.7 1.8* 0.41 0.74 1.8* 0.099 0.096 0.97
Zolpidem
0.29
0.40
1.4*
0.37
0.44
1.2
1.3
1.1
0.85
  • N.D., not detected.

  • * p < 0.05, probability of KO/WT ratio >1.

  • ** p < 0.05, probability of KO/WT ratio >2.

  • a Determined as metabolite formed following carisoprodol administration.