Clinical Trials with Drugs Targeting Ionic Channels, Antiporters, and Pumps in Ischemic Stroke

Spinali, Alessandra; Pignataro, Giuseppe; Renzo, Gianfranco Di; Annunziato, Lucio

doi:10.1007/978-1-60761-280-3_13

Cited by 1 publication

(2 citation statements)

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“…Most trials have focused on calcium and sodium channel blockers, γ-aminobutyric acid agonists and glutamate receptor antagonists, and potassium channel activators, drugs that are all focused on maintaining ion gradients and physiological levels of glutamate. 25,39 Understanding transporter targeting at the BBB during each stage of H/RI offers a novel approach to attain therapeutic goals of neuroprotection for stroke treatment by achieving free concentrations of drugs in the brain that are pharmacologically effective. 32,38,40,41,45,47,48 Such knowledge can be attained by considering currently marketed drugs with neuroprotective properties that are also known substrates for endogenous BBB transporters (ie, statins, memantine).…”

Section: Limitations and Pitfalls Of Current Stroke Therapymentioning

confidence: 99%

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Role of Transporters in Central Nervous System Drug Delivery and Blood-Brain Barrier Protection: Relevance to Treatment of Stroke

Brzica

Abdullahi

Ibbotson

et al. 2017

J Cent Nerv Syst Dis

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Ischemic stroke is a leading cause of morbidity and mortality in the United States. The only approved pharmacologic treatment for ischemic stroke is thrombolysis via recombinant tissue plasminogen activator (r-tPA). A short therapeutic window and serious adverse events (ie, hemorrhage, excitotoxicity) greatly limit r-tPA therapy, which indicates an essential need to develop novel stroke treatment paradigms. Transporters expressed at the blood-brain barrier (BBB) provide a significant opportunity to advance stroke therapy via central nervous system delivery of drugs that have neuroprotective properties. Examples of such transporters include organic anion–transporting polypeptides (Oatps) and organic cation transporters (Octs). In addition, multidrug resistance proteins (Mrps) are transporter targets in brain microvascular endothelial cells that can be exploited to preserve BBB integrity in the setting of stroke. Here, we review current knowledge on stroke pharmacotherapy and demonstrate how endogenous BBB transporters can be targeted for improvement of ischemic stroke treatment.

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Section: Limitations and Pitfalls Of Current Stroke Therapymentioning

confidence: 99%

“…In addition to these changes, there is a significant upregulation of transporters, including luminal Abcb1 and aluminal/abluminal Oatp1a4 that can affect drug delivery across the BBB during H/RI. [38][39][40][41] Figure is an original and previously unpublished drawing.…”

Section: Neuroprotective Properties Of Statinsmentioning

confidence: 99%