Blood-brain barrier: mechanisms governing permeability and interaction with peripherally acting μ-opioid receptor antagonists.

Publication/Presentation Date

9-1-2020

Abstract

The blood-brain barrier (BBB) describes the unique properties of endothelial cells (ECs) that line the central nervous system (CNS) microvasculature. The BBB supports CNS homeostasis via EC-associated transport of ions, nutrients, proteins and waste products between the brain and blood. These transport mechanisms also serve as physiological barriers to pathogens, toxins and xenobiotics to prevent them from contacting neural tissue. The mechanisms that govern BBB permeability pose a challenge to drug design for CNS disorders, including pain, but can be exploited to limit the effects of a drug to the periphery, as in the design of the peripherally acting μ-opioid receptor antagonists (PAMORAs) used to treat opioid-induced constipation. Here, we describe BBB physiology, drug properties that affect BBB penetrance and how data from randomized clinical trials of PAMORAs improve our understanding of BBB permeability.

Volume

45

Issue

9

First Page

688

Last Page

695

ISSN

1532-8651

Disciplines

Medicine and Health Sciences

PubMedID

32723840

Department(s)

Fellows and Residents

Document Type

Article

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