Figure S1. Chemical space of training set and its applicability for prediction of the test set. The grey sphere shows the 95% confidence interval of the chemical variation of the training set explained by the first three principal components, which together explain 66% of the chemical variation of the training set. The test set was found to be well spread throughout the chemical space covered by the training set (shown as the red spheres), except for the outlier teicoplanin, an antibacterial mycin.
Table SI.Compounds included in the test set. High CNS exposure (CNS exp class 1) is defined as brain to plasma ratio of ≥0.3. All compounds with a brain to plasma ratio <0.3 are sorted in the low CNS exposure class (CNS exp class -1).
Compound / CNS exp class / Species/model / Support for classification / Reference
1 / Acamprosate / -1 / mouse, rabbit / Brain to plasma ratio of 0.03 (mouse) and 0.16 (rabbit) / Courtyn et al., Nuclear Med Biol 2004
2 / Acarbose / -1 / rat, dog / Conclude that the BBB permeability was very low / Ahr et al., Arzneimittelforschung 1989
3 / Acrivastine / -1 / rat / Brain to plasma ratio 0.07 / Mahar Doan et al., Pharmacology 1994
4 / Acyclovir / -1 / rat
BBMEC / Brain to plasma ratio for three rats low but highly variable (~0.05, 0.2 and 0.5)
BBB permeability determined to be low / Ståhle &Oberg, Antimicrob Agents Chemother 1992
Shah et al, Pharm Res 1989
5 / Adefovir dipivoxil / -1 / rat, dog, monkey / Conclude poor penetration to CNS /
6 / Alfentanil / -1 / mouse / Brain to plasma ratio of 0.19 / Kalvass et al., Drug Metab Dispos 2005
7 / Almotriptan / -1 / rat
guinea pig / Conclude low distribution to brain
Conclude low distribution to brain / Aubets et al., Xenobiotica 2006
Gras et al, Arzneimittelforschung 2001
8 / Ambenonium / -1 / Statement: does not permeate the BBB / Bolognesi et al., Il Farmaci, 2003
9 / Amoxicillin / -1 / human / Brain to plasma ratio of 0.14 (PB model) / Tod et al., Pharm Res 2008
10 / Amprenavir / -1 / mouse
rat / Brain to plasma ratio of 0.07
Brain to plasma ratio of 0.08 / Kalvass et al., Drug Metab Dispos 2005
Edwards et al., Antimicrob Agents Chemother 2002
11 / Atenolol / -1 / rat / Brain to plasma ratio of 0.16
Brain to plasma ratio of 0.07 / Hakkarainen et al., Int J Pharm 2010
Fridén et al., J Med Chem 2009
12 / Atorvastatin / -1 / mouse / Brain to plasma ratio of 0.04 / Chen et al, Drug Metab Dispos 2007
13 / Atovaquone / -1 / mouse / Brain to sera ratio of 0.06 / Dunay et al., Antimicrob Agents Chemother 2004
14 / Azathioprine / -1 / Statement: Very small amounts reach the brain / Therapeutic Drugs (1991), editor C. Dollery, Churchill Livingstone
15 / Azithromycin / -1 / Statement: Does not distribute to CNS / Goodman and Gilman’s The Pharmacological Basis of Therapeutics (10th ed), Eds Hardman and Limbird, McGrowth-Hall Medical Publishing 2001
16 / Baclofen / -1 / rat / Brain to plasma ratio of 0.08
Brain to plasma ratio of 0.03 / Hakkarainen et al., Int J Pharm 2010
Fridén at el., J Med Chem 2009
17 / Benazepril / -1 / rat, dog, baboon / Statement: Passage of the BBB occur to a minimal extent / Waldmeier & Schmid, Arzneimittelforschung 1984
18 / Benserazide / -1 / rat / Brain to plasma ratio of 0.01 / Schwartz et al., Eur J Clin Pharmacol 1974
19 / Bicalutamide / -1 / rat / Brain to plasma ratio <0.3 / Freeman et al., Br J Cancer 1989
20 / Biotin / -1 / rat / Brain to plasma ratio<0.3 in spite of using brain targeting vehicle / Kang & Pardridge, J Pharmacol Exp Therapeut 1994
21 / Bromocriptine / -1 / mouse / Brain to plasma ratio ~0.2 / Vautier et al., Eur J Pharm Sci 2006
22 / Cabergoline / -1 / rat / Brain to plasma ratio 0.03 / Sharma et al., AAPS Pharm Tech 2009
23 / Captopril / -1 / rat / Statement: Not detected in brain / Migdalof et al., Drug Met Rev 1984
24 / Carbidopa / -1 / Statement: Does not permeate the BBB / FASS – the Swedish PDR (
25 / Cefalexin / -1 / mouse / Statement: Not detected in brain / Klimova Antiobiotiki 1979
26 / Cefdinir / -1 / rat / Statement: Does not distribute to brain / NDA downloaded from FDA:
nda/97/050739s000_050749s000_Omnicef_pharmr.pdf
27 / Ceftriaxone / -1 / rat / Brain to plasma ratio <0.01
28 / Cefuroxime / -1 / rat / AUCbrain/AUCplasma of 0.04
Statement: Distributes to CSF in meningitis / Tsai et al., J Chroatogra B Biomed Sci Appl 1999
FASS – the Swedish PDR (
29 / Cephaloridine / -1 / Statement: Does not cross the BBB / Lecture Notes on Clinical Pharmacology, Authors Reid, Rubin, Whiting. Oxford: Blackwell Science 2001
30 / Cetirizine / -1 / mouse
guinea pig / Brain to plasma ratio 0.02
Brain to plasma ratio 0.22 / Chen et al, Drug Metab Dispos 2003
Gupta et al., Drug Metab Dispos 2006
31 / Cimetidine / -1 / Brain to blood ratio of 0.04 / Salminen et al., J Pharm Biomed Anal 1997
32 / Clindamycin / -1 / Statement: Does not permeate a normal BBB / FASS – the Swedish PDR (
33 / Delaviridine / -1 / rat / Brain to plasma ratio of 0.03 / Fridén et al., J Med Chem 2009
34 / Desloratadine / -1 / Statement: Restricted distribution to CNS / FASS – the Swedish PDR (
35 / Diclofenac / -1 / mouse / Brain to plasma ratio 0.02 / Summerfield et al, J Pharmacol Exp Therapeut 2006
36 / Diflunisal / -1 / rat / Brain to plasma ratio 0.05 / Grace et al., Inflammapharmacol 2000
37 / Dihydrostreptomycin / -1 / Statements: Very poor membrane permeability, Vd equals V of extracellular fluid and very poor CSF distribution /
38 / Dipyridamole / -1 / Statement: Does not permeate BBB / Product specifications
39 / Doxorubicin / -1 / Statement: Does not permeate BBB / Goodman and Gilman’s The Pharmacological Basis of Therapeutics (10th ed), Eds Hardman and Limbird, McGrowth-Hall Medical Publishing 2001
40 / Doxycycline / -1 / rat / Statement: Insignificant fraction crosses BBB / Michel et al., J drug Net Pharmacokinet 1984
41 / Enalaprilate / -1 / Statement: Does not permeate BBB / Product specifications
42 / Ergocalciferol / -1 / rat / Statement: Low distribution to brain / Cruickshank et al, Biochem J 1954
43 / Ergotamine / -1 / Statement: Penetration of the BBB has been questioned or denied / Evers et al., Psychopharmacol 1999
44 / Erythromycin / -1 / Statement: Non significant permeation through BBB / FASS – the Swedish PDR (
45 / Ethambutol / -1 / Not detectable in CSF of healthy patients
Statement: Low BBB permeation / Barling & Selkon, Antimicrob Chemother 1978
apoethambutoltab.pdf
46 / Etinylestradiol / -1 / rat / Brain to plasma ratio of 0.14 / Berry et al., Drug Metab Dispos 2010
47 / Etidronate / -1 / mouse / Statement: Minimal concentration in brain / Mönkkönen et al., Pharmacol Toxicol 1989
48 / Etoposide / -1 / mouse human / Low levels found in brain
Not detectable in CSF / Broggini et al., Cancer Treat Rep 1983
D’Incalci et al., Cancer Chemother Pharmacol 1982
49 / Felbamate / -1 / rat / Brain to plasma ratio of 0.1 / Potschka et al., Epilepsia 2003
50 / Fexofenadine / -1 / rat / Brain to plasma ratio of 0.02 / Mahar Doan et al., Pharmacology 1994
51 / Fluorouracil / -1 / rat / Brain to plasma ratio ~0.12 / Sakane et al., J Drug Target 1999
52 / Fluvastatin / -1 / rat / Not detectable in brain, low but detectable concentration after perfusion / Guillot et al., J Cardiovasc Pharmacol 1993
53 / Fosamprenavir / -1 / Statement: Poor penetration of BBB / Goodman and Gilman’s The Pharmacological Basis of Therapeutics (10th ed), Eds Hardman and Limbird, McGrowth-Hall Medical Publishing 2001
54 / Furosemide / -1 / rat / Brain to plasma ratio of 0.03 / Seno et al, J Pharm Sci 1969
55 / Fusidic acid / -1 / Statement: Does not permeate BBB / FASS – the Swedish PDR (
56 / Ganciclovir / -1 / rat / Brain to plasma ratio of 0.06 / Brewster et al., Antimicrob Agents Chemother 1994
57 / Glimepiride / -1 / Statement: Low passage over BBB / FASS – the Swedish PDR (
58 / Glipizide / -1 / mouse / Not distributed to brain / Goldaniga et al., Arzneimittelforschung 1973
59 / Glucosamine / -1 / rat / Low concentration in brain / Thorell et al., Appl Rad Isotop 1993
60 / Halofuginone / -1 / mouse / Not detected in brain / Stecklair et al., Cancer Chemother Pharmacol 2001
61 / Hydrochlorothiazide / -1 / Statement: Does not permeate BBB / Product specifications
62 / Hydroxycarbamide / -1 / guinea pig / Brain to plasma ratio <0.1 / Dogruel et al., J Neurochem 2003
63 / Indinavir / -1 / mouse / Brain to plasma ratio of 0.08 / Kalvass et al., Drug Metab Dispos 2005
64 / Indomethacin / -1 / rat / Brain to plasma ratio of 0.01 / Fridén et al., J Med Chem 2009
65 / Itraconazole / -1 / mouse / AUCbrain/AUCplasma of 0.16 / Imbert et al., Drug Metab Dispos 2003
66 / Ivermectin / -1 / mouse / Brain to plasma ratio ~0.03 / Kiki-Mvouaka et al, Drug Metab Dispos 2010
67 / Ketoconazole / -1 / mouse / Brain to plasma ratio of 0.20
Statement: Does not cross intact BBB / Choo et al., Drug Metab Dispos 2000
Daneshmend & Warnock, Clin Pharmacokin 1988
68 / Ketoprofen / -1 / mouse / AUCbrain/AUCplasma of 0.02 / Deguchi et al., J Drug Target 2000
69 / Levodopa / -1 / monkey / Brain to plasma of 0.02. Even if adjusted for metabolism to dopamine, brain to plasma ratio <0.3 / Nomoto et al., Parkinsonism Relat Disord 2009
70 / Levofloxacin / -1 / rat / Brain to plasma ratio of 0.17 / Fridén et al., J Med Chem 2009
71 / Lopinavir / -1 / Poor penetration of BBB / Goodman and Gilman’s The Pharmacological Basis of Therapeutics (10th ed), Eds Hardman and Limbird, McGrowth-Hall Medical Publishing 2001
72 / Lufenuron / -1 / Relative low concentrations measured in brain /
73 / M3G / -1 / rat / Brain to plasma ratio of 0.007 / Fridén et al., J Med Chem 2009
74 / M6G / -1 / rat / Brain to plasma ratio of 0.008 / Fridén et al., J Med Chem 2009
75 / Melphalan / -1 / Limited penetration of BBB / FASS – the Swedish PDR (
76 / Mepenzolate / -1 / Does not permeate BBB /
77 / 6-Mercaptopurine / -1 / rat / Brain to plasma ratio of 0.17 / Deguchi et al., Life Sci 2000
78 / Mesalazine / -1 / Does not permeate BBB / Product specifications
79 / Methotrexate / -1 / rat / Brain to plasma ratio of 0.004 / Fridén et al., J Med Chem 2009
80 / Methyldopa / -1 / rat / Brain to plasma ratio <0.3 / Opezzo et al., Pharmacol Res 2000
81 / Metronidazole / -1 / rat / AUCbrain/AUCblood of 0.23 / Tsai and Chen, J Chromatogr A 2003
82 / Mizolastine / -1 / Does not permeate BBB / Product specifications
83 / Moxalactam / -1 / rat / Brain to plasma ratio of 0.003 / Fridén et al., J Med Chem 2009
84 / Moxidectin / -1 / Does not permeate BBB / Product specifications
85 / Nadolol / -1 / rat / Brain to plasma ratio of 0.11 / Fridén et al., J Med Chem 2009
86 / Nelfinavir / -1 / rat / Brain to plasma ratio of 0.04 / Fridén et al., J Med Chem 2009
87 / Nicotinic acid / -1 / rat / Brain to plasma ratio of ~0.02 / Kang et al., J Pharmacobio-Dyn 1990
88 / Nitrofurantoin / -1 / rat / Brain to plasma ratio of 0.008 / Fridén et al., J Med Chem 2009
89 / Norfloxacin / -1 / rat / Brain to plasma ratio of 0.07 / Fridén et al., J Med Chem 2009
90 / Orlistat / -1 / Minimal membrane permeability / Ballinger, Exp Opinion Pharmacother 2000.
91 / Oxytetracycline / -1 / dog / No detectable concentration in brain / Barza et al., Antimicrob Agents Chemother 1975
92 / Paclitaxel / -1 / rat / Brain to plasma ratio of 0.28 / Fridén et al., J Med Chem 2009
93 / PenicillinV / -1 / Low distribution to brain and CSF, in meningitis CSF can reach ~5%. / Product specifications
94 / Phytomenadione / -1 / rat / Low distribution to brain / Thijssen & Drittij-Reijnders, Br J Nutrition 1994
95 / Pivmecillinam / -1 / dog / Brain to sera ratio of 0.02 / Roholt, Antimicrob Chemother 1977
96 / Pyridostigmine / -1 / mouse / Statement: Does not permeate normal BBB / Park et al., EnvironToxPharmacol2008
97 / Raloxifene / -1 / Does not permeate BBB / Goodman and Gilman’s The Pharmacological Basis of Therapeutics (10th ed), Eds Hardman and Limbird, McGrowth-Hall Medical Publishing 2001
98 / Ranitidine / -1 / Brain to blood ratio of 0.06 / Salminen et al., J Pharm Biomed Anal 1997
99 / Retinol / -1 / rat / Brain to plasma ratio <0.05 / Pardridge et al., J Neurochem 1985
100 / Rifampicin / -1 / mouse
rat / Brain to plasma ratio of <0.01
Brain to plasma ratio of 0.03 / Padowski & Pollack, J Pharm Sci 2010
Fridén et al., J Med Chem 2009
101 / Rifapentine / -1 / rabbit / Brain to plasma ratio of 0.18 / Assandri et al., J Antiobiot (Tokyo) 1984
102 / Ritonavir / -1 / mouse / Brain to plasma ratio of 0.04 / Choo et al., Drug Metab Dispos 2000
103 / Rizatriptan / -1 / mouse / Brain to plasma ratio of 0.20 / Evans et al., Drug Metab Dispos 2003
104 / Rosiglitazone / -1 / mouse / Brain to plasma ratio of 0.05 / Festuccia et al., Endocrinology 2008
105 / Rosuvastatin / -1 / rat / Very low uptake in brain / Chapman & McTaggart, Atherosclerosis Suppl 2002
106 / Salicylic acid / -1 / rat / Brain to plasma ratio of 0.05 / Fridén et al., J Med Chem 2009
107 / Streptomycin / -1 / Very poor membrane permeation, low Vd and very poor distribution to CSF /
108 / Sulfamethoxazole / -1 / monkey / Brain to plasma ratio <0.3 / Craig & Kunin, J Infect Dis 1973
109 / Sulphasalazine / -1 / rat / Brain to plasma ratio of 0.005 / Fridén et al., J Med Chem
110 / Sulpiride / -1 / mouse / Brain to plasma ratio of0.08 / Doran et al., Drug Metab Dispos 2005
111 / Sumatriptan / -1 / mouse / Brain to plasma ratio of 0.13 / Kalvass et al., Drug Metab Dispos 2005
112 / Teicoplanin / -1 / Slow diffusion to CSF, no therapeutic concentrations are obtained / FASS – the Swedish PDR (
113 / Telithromycin / -1 / Poor passage through BBB /
114 / Thiamine / -1 / rat / Brain to perfusate ratio of 0.02 (frontal cortex) / Lockman et al., J Neurochem 2003
115 / Thioguanine / -1 / rat / Brain concentration low due to high efflux in BBB / Mori et al., J Neurochem 2004
116 / Toremifene / -1 / Does not penetrate BBB / Goodman and Gilman’s The Pharmacological Basis of Therapeutics (10th ed), Eds Hardman and Limbird, McGrowth-Hall Medical Publishing 2001
117 / Trimethoprim / -1 / monkey / Brain to plasma ratio <0.3 / Tu et al., J Pharm Sci 1989
118 / Valdecoxib / -1 / mouse / Brain to plasma ratio 0.05 / Summerfield et al, J Pharmacol Exp Therapeut 2006
119 / Vigabatrin / -1 / rat / Brain to plasma ratio of 0.1 / Tsong et al., Epilepsia 2003
120 / Warfarin / -1 / rat / Brain to plasma ratio of 0.10 / Urien et al., J Pharmacol Exp Therapeut 1989
121 / Zidovudine / -1 / mouse
rabbit
rat / Brain to plasma ratio of 0.10
Brain to plasma ratio of 0.19
Brain to plasma ratio of 0.065 / Chow et al., Pharm Res 1998
Wang et al., J Pharm Sci 1995
Fridén et al. J Med Chem 2009
122 / Zolmitriptan / -1 / mouse / Brain to plasma ratio or 0.04 / Evans et al., Drug Metab Dispos 2003
123 / Acetaminophen / 1 / Brain to blood ratio of 0.49 / Salminen et al., J Pharm Biomed Anal 2000
124 / Acetylsalicylic acid / 1 / Brain to blood ratio of 0.32 / Salminen et al., J Pharm Biomed Anal 2000
125 / Alimemazine / 1 / human / Brain to plasma ratio of 3.05 (post mortem). N.B. overdose of alimemazine / Kintz et al, J Anal Toxicol 1995
126 / Alprazolam / 1 / Brain to blood ratio of 1.1 / Salminen et al., J Pharm Biomed Anal 2000
127 / Alprenolol / 1 / rat / Brain to plasma ratio of 8.27 / Fridén et al., J Med Chem 2009.
128 / Altretamine / 1 / mouse / Brain to plasma ratio of 3.99 / Broggini et al., Cancer Treat Rep 1982
129 / Amitriptyline / 1 / mouse
rat / Brain to plasma ratio of ~25
Brain to plasma ratio of 20.15 / Abaut et al., Int J Pharm 2009
Fridén et al., J Med Chem 2009
130 / Aripiprazole / 1 / rat / Brain to plasma ratio of ~5 / Shimokawa, J Chromatogr B Analyt Technol Biomed Life Sci 2005
131 / Ascorbic acid / 1 / rat / Brain to plasma ratio of ~3 / van der Loo et al., Biochim Biophys Res Commun 2003
132 / Biperiden / 1 / rat / Brain to plasma ratio of 13 / Ishizaki et al., J Pharm Pharmacol 1998
133 / Bupropion / 1 / rat / Brain to plasma ratio of ~25
Brain to plasma ratio of 9.78 / Schroeder et al., J Clin Psych 1983
Fridén et al., J Med Chem 2009
134 / Buspiron / 1 / mouse / Brain to plasma ratio of 1.6 / Doran et al., Drug Metab Dispos 2005
135 / Carbamazepine / 1 / mouse / Brain to plasma ratio of 0.76 / Doran et al., Drug Metab Dispos 2005
136 / Carisoprodol / 1 / mouse / Brain to plasma ratio of 0.66 / Doran et al., Drug Metab Dispos 2005
137 / Celecoxib / 1 / rat / Brain to plasma ratio of 1.7 / Okumura et al., Eur J Pharmacol 2006
138 / Chlorcyclizine / 1 / rat / Brain to plasma ratio of 15 / Kuntzman et al., J Pharmacol Exp Therapeut 1965
139 / Chloroquine / 1 / Statement: Brain concentration can be 10-30 fold higher than plasma / Telgt et al., Ann Pharmacother 2005
140 / Chlorpromazine / 1 / Brain to blood ratio of 11.5 / Salminen et al., J Pharm Biomed Anal 2000
141 / Chlorzoxazone / 1 / rat / Brain to plasma ratio of 1 / Yasuhara & Levy, Pharm Res 1995
142 / Citalopram / 1 / mouse / Brain to plasma ratio of 5.1 / Doran et al., Drug Metab Dispos 2005
143 / Clemastine / 1 / rat / High penetration into brain / Obradovic et al., Pharm Res 2007
144 / Clomethiazole / 1 / gerbil / Brain to plasma ratio of 1.4 / Green et al., Br J Pharmacol 2000
145 / Clompiramine / 1 / rat / Brain to plasma ratio of 22 / Kurata et al., Jpn J Psychiatry Neurol 1986
146 / Clonazepam / 1 / rat / Brain to plasma ratio 0.3 at time≥1h / Vyas et al., J Pharm Sci 2006
147 / Clonidine / 1 / Brain to blood ratio of 1.3 / Salminen et al., J Pharm Biomed Anal 2000
148 / Clozapine / 1 / mouse
rat / Brain to plasma ratio of 4.1
Brain to plasma ratio of 10.2 / Doran et al., Drug Metab Dispos 2005
Zhang et al., J Chromatogr B 2007
149 / Codeine / 1 / rat / Brain to plasma ratio of 2.70 / Fridén et al., J Med Chem 2009
150 / Cyclobenzaprine / 1 / mouse / Brain to plasma ratio of 12 / Doran et al., Drug Metab Dispos 2005
151 / Cyclophosphamide / 1 / Brain to plasma of ~1 / Product specifications
152 / Deferiprone / 1 / rat / Brain to plasma ratio >0.7 / Fredenburg et al., Toxicol 1986
153 / Dexamethasone / 1 / mouse / Brain to plasma ratio of 0.30 / Kalvass et al., Drug Metab Dispos 2005
154 / Dextropropoxyphene / 1 / rat / Brain to plasma ratio of 4.4 / Due et al., Toxicol Appl Pharmacol 1981
155 / Diphenhydramine / 1 / rat / Brain to plasma ratio of 16.25 / Fridén et al., J Med Chem 2009
156 / Donepzil / 1 / rat / Brain to plasma ratio >2 (dose dependent) / Kim et al, J Pharm Sci 2009
157 / Eletriptan / 1 / mouse / Brain to plasma ratio of 0.30 / Evans et al, Drug Metab Dispos 2003
158 / Enrofloxacin / 1 / canine / Brain to plasma ratio of 0.37 / Product specifications
159 / Ethosuximide / 1 / mouse / Brain to plasma ratio of 1.1 / Doran et al., Drug Metab Dispos 2005
160 / Ethyl-phenylmalonamide / 1 / rat / Brain to plasma ratio of 0.64 / Fridén et al., J Med Chem 2009
161 / Etoricoxib / 1 / mouse / Brain to plasma ratio of 0.66 / Summerfield et al, J Pharmacol Exp Therapeut 2006
162 / Fentanyl / 1 / mouse / Brain to plasma ratio of 2.4 / Kalvass et al., Drug Metab Dispos 2005
163 / Fluconazole / 1 / human / Brain to blood ratio of 1.3 (PET) / Fischman et al., Antimicrob Agents Chemother 1993
164 / Flunitrazepam / 1 / rat / Brain to plasma >1 / Becherucci et al., Pharmacol Res Commun 1985
165 / Fluoxetine / 1 / mouse / Brain to plasma ratio of 12 / Doran et al., Drug Metab Dispos 2005
166 / Fluphenazine / 1 / rat / Brain to plasma >10 / Aravagiri et al., Neuropsychopharmacol 1995
167 / Fluvoxamine / 1 / mouse / Brain to plasma ratio of 6.1 / Doran et al., Drug Metab Dispos 2005
168 / Gabapentin / 1 / rat / Brain to blood ratio of 0.75
Brain to plasma ratio of 0.64 / Wang & Welty, Pharm Res 1996
Fridén et al., J Med Chem 2009
169 / Galantamine / 1 / mouse / Brain to plasma ratio of 2.1 / Bickel et al., Neuropharmacology 1991
170 / Granisetron / 1 / rat / Brain to plasma ratio >0.3 / Huang et al., Life Sci 1999
171 / Haloperidol / 1 / mouse
rat / Brain to plasma ratio of 13
Brain to plasma ratio of 18 / Doran et al., Drug Metab Dispos 2005
Zhang et al., J Chromatogr B 2007
172 / Hydrocodone / 1 / mouse / Brain to plasma ratio of 2.1 / Doran et al., Drug Metab Dispos 2005
173 / Hydroxychloroquine / 1 / rat / Brain to plasma ration of ~2 / Wei et al, Chirality 1995
174 / Hydroxyzine / 1 / mouse / Brain to plasma ratio of 7.7 / Doran et al., Drug Metab Dispos 2005
175 / Hyoscyamine / 1 / mouse / Brain to plasma ratio of 0.7 / Palmer et al., Acta Pharmacol et Toxicol 1981
176 / Isoniazid / 1 / baboon / Brain to plasma ~1 (PET) / Liu et al. J Med Chem 2010
177 / Lamotrigine / 1 / mouse
rat / Brain to plasma ratio of 1.1
Brain to plasma ratio of 2.02 / Doran et al., Drug Metab Dispos 2005
Fridén et al., J Med Chem 2009
178 / Levetiracetam / 1 / rat / Brain to serum ratio of 0.5 / Tong & Patsalos, Br J Pharmacol 2001
179 / Levomepromazine / 1 / human / Brain to plasma ratio >10 (post mortem) / Kornhuber, J Neural Transm 2006
180 / Lidocaine / 1 / rat / Brain to plasma ratio of 1.6 / Berry et al., Drug Metab Dispos 2010
181 / Linezolid / 1 / human / Brain to serum ratio of 0.45 / Tsona et al., J Chemother 2010
182 / Loratadine / 1 / mouse / Brain to plasma ratio of 1.6 / Uchida et al, J Pharmacol Exp Therapeut 2011
183 / Lorazepam / 1 / human / Brain to plasma ratio >0.57 / Greenblatt et al, Pharm Exp Therapeut 1989
184 / Maprotiline / 1 / rat / AUCbrain/AUCserum of 57 / Miyake et al., J Pharm Sci 1992
185 / Mefloquine / 1 / mouse / Brain to plasma ratio of 1.31 / de Lagerie, Drug Metab Lett 2009
186 / Melperone / 1 / mouse / Brain to plasma ratio of 6.7 / Uhr et al., J Psychopharmacol 2004
187 / Memantine / 1 / mouse
rat / Brain to plasma ratio of 30
Brain to plasma ratio >10 / Saab & Roder, Pharmacol 2011
Wesemann, Arzneimittelforschung 1989
188 / Meprobamate / 1 / mouse / Brain to plasma ratio of 0.42 / Doran et al., Drug Metab Dispos 2005
189 / Methadon / 1 / mouse / Brain to plasma ratio of 2 / Kalvass et al., Drug Metab Dispos 2007
190 / Methylphenidate / 1 / mouse / Brain to plasma ratio of 12 / Doran et al., Drug Metab Dispos 2005
191 / Metoclopramide / 1 / mouse / Brain to plasma ratio of 1.2 / Doran et al., Drug Metab Dispos 2005
192 / Metoprolol / 1 / rat / Brain to plasma ratio of 0.57
Brain to plasma ratio of 3.14 / Berry et al., Drug Metab Dispos 2010
Fridén et al., J Med Chem 2009
193 / Mianserin / 1 / mouse / Cmax,Brain/Cmax, Plasma >10 / Alta mura et al., Prog Neuropsychopharmacol Biol Psychiatry 1987
194 / Midazolam / 1 / Brain to blood ratio of 2.3 / Salminen et al., J Pharm Biomed Anal 2000
195 / Mirtazepine / 1 / human / Brain to plasma ratio of ~10 (PET) / Smith et al., J Psychopharmacol 2008
196 / Modafinil / 1 / rat / Brain to plasma ratio >0.3 / Waters et al., J Psychopharmacol 2005
197 / Morphine / 1 / mouse
rat
rat / Brain to plasma ratio of 0.46
Brain to plasma ratio of 0.56
Brain to plasma ratio of 0.51 / Doran et al., Drug Metab Dispos 2005
Bostrom et al., Anesthesiology 2008
Fridén et al., J Med Chem 2009
198 / Naltrexone / 1 / rat / Brain to plasma ratio of 0.83 / Berry et al., Drug Metab Dispos 2010
199 / Naratriptan / 1 / mouse / Brain to plasma ratio of 0.42 / Kalvass et al., Drug Metab Dispos 2005
200 / Nevirapine / 1 / guinea pig / Brain to plasma ratio >0.3 / Gibbs et al., J Pharmacol Exp Therapeut 2006
201 / Nitrazepam / 1 / human / Brain to plasma ratio >0.3 (post mortem) / Moriya & Hashimoto, Forensic Sci Int
202 / Norptriptyline / 1 / mouse / Brain to plasma ratio of 11 / Doran et al., Drug Metab Dispos 2005
203 / Olanzapine / 1 / rat / Brain to plasma ratio >5 / Aravagiri et al., Biopharm Drug Dispos 1999
204 / Oxazepam / 1 / rat / Brain to plasma ratio >5 / Sisenwine & Tio, Drug metab Dispos 1986
205 / Oxprenolol / 1 / rat / Brain to plasma ratio of 1.06 / Fridén et al., J Med Chem 2009
206 / Oxybutynin / 1 / rat / Brain to plasma ratio of 6.27 / Callegari et al., Br J Clin Pharmacol 2011
207 / Oxycodone / 1 / rat / Brain to plasma ratio of 3
Brain to plasma ratio of 3.77 / Boström et al., Anesthesiology 2008
Fridén et al., J Med Chem 2009
208 / Oxymorphone / 1 / rat / Brain to plasma ratio of 2.29 / Fridén et al., J Med Chem 2009
209 / Paroxetine / 1 / mouse / Brain to plasma ratio of 3.3 / Doran et al., Drug Metab Dispos 2005
210 / Pentobarbital / 1 / Brain to blood ratio of 1.32 / Salminen et al., J Pharm Biomed Anal 2000
211 / Perphenazine / 1 / human / Brain to blood ratio of ~3 (post mortem) / Levine et al., J Anal Toxicol 1999
212 / Pethidine / 1 / mouse / Brain to plasma ratio of 6.8 / Kalvass et al., J Pharmacol Exp Therapeut 2007
213 / Phenobarbital / 1 / rat / Brain to plasma ratio of 0.72 / Leppik & Sherwin, Epilepsia 1979
214 / Phenylalanine / 1 / mouse, rat / Brain to plasma ratio of ~1.2 (mouse) and ~2 (rat) / Murakami et al., Am J Physiol Heart Circ Phys 2000
215 / Pindolol / 1 / rat / Brain to plasma ratio of 1.56
Brain to plasma ratio of ~4 / Fridén et al., J Med Chem 2009
Garvey & Ram, J Pharmacol Exp Therapeut 1975
Yan & Lewander, Eur Neiropsychopharmacol 1999
216 / Piracetam / 1 / rat / Brain to plasma ratio of ~1 / Tacconi & Wurtman, J Pharm Pharmacol 1984
217 / Prochlorperazine / Statement: High concentrations reach the brain / (accessed Jan 26 2012)
218 / Promazine / 1 / Brain to blood ratio of 17 / Salminen et al., J Pharm Biomed Anal 2000
219 / Promethazine / 1 / rabbit / Brain to plasma ratio of 20 / Yokogawa et al., Pharm Res 1990
220 / Propoxyphene / 1 / mouse / Brain to plasma ratio of 2.9 / Doran et al., Drug Metab Dispos 2005
221 / Pyrazinamide / 1 / baboon / Brain to plasma ratio of ~1.4 (PET) / Liu et al. J Med Chem 2010
222 / Pyrilamine / 1 / Brain to blood ratio of 3.16 / Salminen et al., J Pharm Biomed Anal 2000
223 / Quetiapine / 1 / human / Brain to plasma ratio of ~2 (post mortem) / Hopenwasser et al., J Anal Toxicol 2004
224 / Reboxetine / 1 / mouse, rat / Brain to plasma ratio of >1 / Strolin Benedetti et al., Chirality 1995
225 / Rifabutin / 1 / rat / Brain to plasma ratio 0.57 / Battaglia et al., Antimicrob Agents Chemother 1991
226 / Riluzole / 1 / mouse / Brain to plasma ratio of 2.4 / Milane et al., J Pharm Pharmaceut Sci 2009
227 / Risperidone / 1 / mouse
rat / Brain to plasma ratio of 0.78
Brain to plasma ratio of 0.48 / Doran et al., Drug Metab Dispos 2005
Zhang et al., J Chromatogr B 2007
228 / Rivastigmine / 1 / rat / AUCbrain/AUCplasma of 3.1 / Arumugam et al., Acta Pharm 2008
229 / Rofecoxib / 1 / rat / Brain to plasma ratio of 0.47 / Okumura et al., Eur J Pharmacol 2006
230 / Selegiline / 1 / mouse / Brain to plasma ratio of 3.7 / Doran et al., Drug Metab Dispos 2005
231 / Sertraline / 1 / mouse / Brain to plasma ratio of 24 / Doran et al., Drug Metab Dispos 2005
232 / Sildenafil / 1 / human / Brain to blood >100 (post mortem) / Pagani et al., J Anal Toxicol 2005
233 / Sulfentanil / 1 / mouse / Brain to plasma ratio of 1.6 / Kalvass et al., Drug Metab Dispos 2005
234 / Tacrine / 1 / rat / Brain to plasma ratio of 9.56 / Fridén et al., J Med Chem 2009
235 / Temazolide / 1 / rat / Brain to plasma ratio of 0.35 / Reyderman et al., Xenobiotica 2004
236 / Theophylline / 1 / Brain to blood ratio of 0.52 / Salminen et al., J Pharm Biomed Anal 2000
237 / Thiopental / 1 / mouse
rat / Brain to plasma ratio of 0.36
Brain to plasma ratio of 1.28 / Doran et al., Drug Metab Dispos 2005
Fridén et al., J Med Chem 2009
238 / Thioridazine / 1 / rat / Brain to plasma ratio of 3.75 / Fridén et al., J Med Chem 2009
239 / Tinidazole / 1 / rat / Brain to plasma ratio of 0.69 / Wood et al., J Antimicrob Chemother 1982
240 / Topiramate / 1 / rat / Brain to plasma ratio of 0.4
Brain to plasma ratio of 0.84 /
Fridén et al., J Med Chem 2009
241 / Tramadol / 1 / mouse
rat / Brain to plasma ratio >1 (mouse) and >2 (rat)
Brain to plasma ratio of 5.29 / Tao et al., J Clin Pharm Ther 2002
Fridén et al., J Med Chem 2009
242 / Trazodone / 1 / mouse / Brain to plasma ratio of 0.61 / Doran et al., Drug Metab Dispos 2005
243 / Triazolam / 1 / rat / AUCbrain/AUCplasma of 0.31 / Nakashima et al., J Pharm Biomed Anal 2003
244 / Trihexyphenidyl / 1 / rat / Brain to plasma ratio of 13.7 / Ischizaki et al., J Pharm Pharmacol 1998
245 / Trimipramine / 1 / mouse / Brain to plasma ratio of 7 / Ur et al., J Psych Res 2003
246 / Triprolidine / 1 / mouse / Brain to plasma ratio of 5.9 / Kalvass et al., Drug Metab Dispos 2005
247 / Venlafaxine / 1 / mouse / Brainto plasma ratio of 4.2 / Doran et al., Drug Metab Dispos 2005
248 / Vinblastine / 1 / mouse / Brain to plasma ratio of 1.7 / Kalvass et al., Drug Metab Dispos 2005
249 / Ziprasidone / 1 / rat / Brain to plasma ratio of 2.38 / Zhang et al., J Chromatogr B 2007
250 / Zolpidem / 1 / mouse
rat / Brain to plasma ratio of 0.29
Brain to plasma ratio of 0.32 / Doran et al., Drug Metab Dispos 2005
Trenque et al., J Pharm Pharmacol 1994
251 / Zopiclone / 1 / rat / Brain to plasma ratio >0.3 / Fernandez et al., J Pharm Pharmacol 2002
BBMEC = bovine brain microvascular endothelial cells