Pharmaceuticals 2013, 6(10), 1287-1303; doi:10.3390/ph6101287

Glibenclamide for the Treatment of Acute CNS Injury

1email, 1email, 1email, 1email, 1email, 1email and 1,2,3,* email
Received: 16 July 2013; in revised form: 17 September 2013 / Accepted: 23 September 2013 / Published: 11 October 2013
(This article belongs to the Special Issue CNS-Drugs and Therapy)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: First introduced into clinical practice in 1969, glibenclamide (US adopted name, glyburide) is known best for its use in the treatment of diabetes mellitus type 2, where it is used to promote the release of insulin by blocking pancreatic KATP [sulfonylurea receptor 1 (Sur1)-Kir6.2] channels. During the last decade, glibenclamide has received renewed attention due to its pleiotropic protective effects in acute CNS injury. Acting via inhibition of the recently characterized Sur1-Trpm4 channel (formerly, the Sur1-regulated NCCa-ATP channel) and, in some cases, via brain KATP channels, glibenclamide has been shown to be beneficial in several clinically relevant rodent models of ischemic and hemorrhagic stroke, traumatic brain injury, spinal cord injury, neonatal encephalopathy of prematurity, and metastatic brain tumor. Glibenclamide acts on microvessels to reduce edema formation and secondary hemorrhage, it inhibits necrotic cell death, it exerts potent anti-inflammatory effects and it promotes neurogenesis—all via inhibition of Sur1. Two clinical trials, one in TBI and one in stroke, currently are underway. These recent findings, which implicate Sur1 in a number of acute pathological conditions involving the CNS, present new opportunities to use glibenclamide, a well-known, safe pharmaceutical agent, for medical conditions that heretofore had few or no treatment options.
Keywords: glibenclamide; Sur1-Trpm4 channel; cerebral ischemia; traumatic brain injury; spinal cord injury; encephalopathy of prematurity; metastatic brain tumor
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MDPI and ACS Style

Kurland, D.B.; Tosun, C.; Pampori, A.; Karimy, J.K.; Caffes, N.M.; Gerzanich, V.; Simard, J.M. Glibenclamide for the Treatment of Acute CNS Injury. Pharmaceuticals 2013, 6, 1287-1303.

AMA Style

Kurland DB, Tosun C, Pampori A, Karimy JK, Caffes NM, Gerzanich V, Simard JM. Glibenclamide for the Treatment of Acute CNS Injury. Pharmaceuticals. 2013; 6(10):1287-1303.

Chicago/Turabian Style

Kurland, David B.; Tosun, Cigdem; Pampori, Adam; Karimy, Jason K.; Caffes, Nicholas M.; Gerzanich, Volodymyr; Simard, J. M. 2013. "Glibenclamide for the Treatment of Acute CNS Injury." Pharmaceuticals 6, no. 10: 1287-1303.

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