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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Review Article

Transient Opening of the Blood-Brain Barrier by Vasoactive Peptides to Increase CNS Drug Delivery: Reality Versus Wishful Thinking?

Author(s): Matthew A. Smith-Cohn*, Nicholas B. Burley and Stuart A. Grossman*

Volume 20, Issue 7, 2022

Published on: 11 May, 2022

Page: [1383 - 1399] Pages: 17

DOI: 10.2174/1570159X20999220131163504

Price: $65

Abstract

Background: The blood-brain barrier inhibits the central nervous system penetration of 98% of small molecule drugs and virtually all biologic agents, which has limited progress in treating neurologic disease. Vasoactive peptides have been shown in animal studies to transiently disrupt the blood-brain barrier and regadenoson is currently being studied in humans to determine if it can improve drug delivery to the brain. However, many other vasoactive peptides could potentially be used for this purpose.

Methods: We performed a review of the literature evaluating the physiologic effects of vasoactive peptides on the vasculature of the brain and systemic organs. To assess the likelihood that a vasoactive peptide might transiently disrupt the blood-brain barrier, we devised a four-tier classification system to organize the available evidence.

Results: We identified 32 vasoactive peptides with potential blood-brain barrier permeabilityaltering properties. To date, none of these are shown to open the blood-brain barrier in humans. Twelve vasoactive peptides increased blood-brain barrier permeability in rodents. The remaining 20 had favorable physiologic effects on blood vessels but lacked specific information on permeability changes to the blood-brain barrier.

Conclusion: Vasoactive peptides remain an understudied class of drugs with the potential to increase drug delivery and improve treatment in patients with brain tumors and other neurologic diseases. Dozens of vasoactive peptides have yet to be formally evaluated for this important clinical effect. This narrative review summarizes the available data on vasoactive peptides, highlighting agents that deserve further in vitro and in vivo investigations.

Keywords: Blood-brain barrier, vasoactive peptides, pharmacokinetics, neurology, neuro-oncology, drug delivery, oncology, metastasis.

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