Glibenclamide for the Treatment of Acute CNS Injury

Pharmaceuticals

David B. Kurland¹  Cigdem Tosun¹  Adam Pampori¹  Jason K. Karimy¹  Nicholas M. Caffes¹  Volodymyr Gerzanich¹ 

[1] Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; E-Mails:

关键词: glibenclamide;    Sur1-Trpm4 channel;    cerebral ischemia;    traumatic brain injury;    spinal cord injury;    encephalopathy of prematurity;    metastatic brain tumor;   

DOI  :  10.3390/ph6101287

来源: mdpi

【 摘 要 】

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 K_ATP [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 NC_Ca-ATP channel) and, in some cases, via brain K_ATP 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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.