Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke
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Affiliation
Univ Arizona, Coll Med, Dept PharmacolIssue Date
2020-02-14Keywords
HMG-CoA reductase inhibitorsblood-brain barrier
Drug Delivery
Neurovascular Unit
Organic anion transporting polypeptides
stroke
Transporter
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MDPICitation
Williams, E.I.; Betterton, R.D.; Davis, T.P.; Ronaldson, P.T. Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke. Pharmaceutics 2020, 12, 154.Journal
PharmaceuticsRights
Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Ischemic stroke is the 5th leading cause of death in the United States. Despite significant improvements in reperfusion therapies, stroke patients still suffer from debilitating neurocognitive deficits. This indicates an essential need to develop novel stroke treatment paradigms. Endogenous uptake transporters expressed at the blood-brain barrier (BBB) provide an excellent opportunity to advance stroke therapy via optimization of small molecule neuroprotective drug delivery to the brain. Examples of such uptake transporters include organic anion transporting polypeptides (OATPs in humans; Oatps in rodents) and organic cation transporters (OCTs in humans; Octs in rodents). Of particular note, small molecule drugs that have neuroprotective properties are known substrates for these transporters and include 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) for OATPs/Oatps and 1-amino-3,5-dimethyladamantane (i.e., memantine) for OCTs/Octs. Here, we review current knowledge on specific BBB transporters that can be targeted for improvement of ischemic stroke treatment and provide state-of-the-art perspectives on the rationale for considering BBB transport properties during discovery/development of stroke therapeutics.Note
Open access journalISSN
1999-4923PubMed ID
32075088Version
Final published versionae974a485f413a2113503eed53cd6c53
10.3390/pharmaceutics12020154
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Except where otherwise noted, this item's license is described as Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).