Multifunctional drugs for head injury.
Traumatic brain injury (TBI) remains one of the leading causes of mortality and morbidity worldwide in individuals under the age of 45 years, and, despite extensive efforts to develop neuroprotective therapies, there has been no successful outcome in any trial of neuroprotection to date. In addition to recognizing that many TBI clinical trials have not been optimally designed to detect potential efficacy, the failures can be attributed largely to the fact that most of the therapies investigated have been targeted toward an individual injury factor. The contemporary view of TBI is that of a very heterogenous type of injury, one that varies widely in etiology, clinical presentation, severity, and pathophysiology. The mechanisms involved in neuronal cell death after TBI involve an interaction of acute and delayed anatomic, molecular, biochemical, and physiological events that are both complex and multifaceted. Accordingly, neuropharmacotherapies need to be targeted at the multiple injury factors that contribute to the secondary injury cascade, and, in so doing, maximize the likelihood of a successful outcome. This review focuses on a number of such multifunctional compounds that have shown considerable success in experimental studies and that show maximum promise for success in clinical trials.
Vink
Robert
R
School of Medical Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia. Vink@adelaide.edu.au
Nimmo
Alan J
AJ
D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D016572:Cyclosporine / Q000627:therapeutic use; D013759:Dronabinol / Q000031:analogs & derivatives / Q000627:therapeutic use; D004921:Erythropoietin / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007705:Kinins / Q000037:antagonists & inhibitors; D008274:Magnesium / Q000627:therapeutic use; D008911:Minocycline / Q000627:therapeutic use; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011374:Progesterone / Q000627:therapeutic use; D011619:Psychotropic Drugs / Q000627:therapeutic use; D013973:Thyrotropin-Releasing Hormone / Q000627:therapeutic use; D051193:Toll-Like Receptors / Q000819:agonists
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007705:Kinins; D018696:Neuroprotective Agents; D011619:Psychotropic Drugs; D051193:Toll-Like Receptors; D004921:Erythropoietin; D011374:Progesterone; D013973:Thyrotropin-Releasing Hormone; D013759:Dronabinol; D016572:Cyclosporine; D008911:Minocycline; D008274:Magnesium; C062018:HU 211