New drugs on the horizon for cerebral edema: what's in the clinical development pipeline?

INTRODUCTION: Research has advanced our understanding of the molecular and cellular mechanisms of cerebral edema and has propelled the development of novel antiedema therapeutics. Current evidence supports aberrant neuro-glial ion transport as a central mechanism that underlies pathological fluid accumulation after central nervous system injury. AREAS COVERED: Novel agents in clinical development show potential in altering the natural history and treatment of cerebral edema. Using the PubMed and Google Scholar databases, we review recent advances in our understanding of cerebral edema and describe agents under active investigation, their mechanism, and their application in recent and ongoing clinical trials. EXPERT OPINION: Pharmacotherapies that target molecular mechanisms underlying the compensatory post-injury response of ion channels and transporters that lead to pathological alteration of osmotic gradients are the most promising therapeutic strategies. Repurposing of drugs such as glyburide that inhibit the aberrant upregulation of ion channels such as SUR1-TRPM4, and novel agents, such as ZT-1a, which reestablish physiological regulation of ion channels such as NKCC1/KCC, could be useful adjuvants to prevent and even reverse fluid accumulation in the brain parenchyma.