The blood-brain barrier: Bottleneck in brain drug development

被引：227

作者：

Pardridge W.M. ^{[1
,2
]}

机构：

[1] Department of Medicine, UCLA, Los Angeles

[2] UCLA Warren Hall, 13-164, Los Angeles, CA 90024

来源：

NeuroRX | 2005年 / 2卷 / 1期

基金：

美国国家卫生研究院;

关键词：

Biological transport; Blood-brain barrier; Drug targeting; Endothelium; Neurotherapeutics;

D O I：

10.1602/neurorx.2.1.3

中图分类号：

学科分类号：

摘要：

The blood-brain barrier (BBB) is formed by the brain capillary endothelium and excludes from the brain ∼100% of large-molecule neurotherapeutics and more than 98% of all small-molecule drugs. Despite the importance of the BBB to the neurotherapeutics mission, the BBB receives insufficient attention in either academic neuroscience or industry programs. The combination of so little effort in developing solutions to the BBB problem, and the minimal BBB transport of the majority of all potential CNS drugs, leads predictably to the present situation in neurotherapeutics, which is that there are few effective treatments for the majority of CNS disorders. This situation can be reversed by an accelerated effort to develop a knowledge base in the fundamental transport properties of the BBB, and the molecular and cellular biology of the brain capillary endothelium. This provides the platform for CNS drug delivery programs, which should be developed in parallel with traditional CNS drug discovery efforts in the molecular neurosciences.

引用

页码：3 / 14

页数：11

共 80 条

[1]

Pardridge W.M., Brain Drug Targeting: The Future of Brain Drug Development, (2001)

[2]

Lloyd K., Hornykiewicz O., Parkinson's disease activity of l-dopa decarboxylase in discrete brain regions, Science, 170, pp. 1212-1213, (1970)

[3]

Zivadinov R., Zorzon M., Tommasi M.A., Nasuelli D., Bernardi M., Monti-Bragadin L., Et al., A longitudinal study of quality of life and side effects in patients with multiple sclerosis treated with interferon β-1a, J Neurol Sci, 216, pp. 113-118, (2003)

[4]

Antinori A., Cingolani A., Giancola M.L., Forbici F., De Luca A., Perno C.F., Clinical implications of HIV-1 drug resistance in the neurological compartment, Scand J Infect Dis Suppl, 106, 35 SUPPL., pp. 41-44, (2003)

[5]

Kandanearatchi A., Williams B., Everall I.P., Assessing the efficacy of highly active antiretroviral therapy in the brain, Brain Pathol, 13, pp. 104-110, (2003)

[6]

Ghose A.K., Viswanadhan V.N., Wendoloski J.J., A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases, J Comb Chem, 1, pp. 55-68, (1999)

[7]

Lipinski C.A., Drug-like properties and the causes of poor solubility and poor permeability, J Pharmacol Toxicol Methods, 44, pp. 235-249, (2000)

[8]

Fischer H., Gottschlich R., Seelig A., Blood-brain barrier permeation molecular parameters governing passive diffusion, J Membr Biol, 165, pp. 201-211, (1998)

[9]

Lieb W.R., Stein W.D., NonStokesian nature of transverse diffusion within human red cell membranes, J Membr Biol, 92, pp. 111-119, (1986)

[10]

Trauble H., The movement of molecules across lipid membranes: A molecular theory, J Membrane Biol, 4, pp. 193-208, (1971)

← 1 2 3 4 5 6 7 8 →