Integrative review of the use of NMDA antagonists for TBI treatment

Abstract

Introduction: The kinetic energy of TBI generates mechanical deformation, which causes release of glutamate, activating ionotropic receptors, principally NMDA receptors, favoring the flow of Ca++ and Na+ into the cell, producing edema. Then, the neurotoxicity generated by glutamate release can be avoided by NMDA antagonists. Objectives: To define if NMDA antagonists are promising for the treatment of TBI by literature analysis and to verify if there are reports of adverse reactions. Methodology: The review utilized the Scielo and Pubmed databases and the keywords used were: NMDA antagonist, Brain edema and Brain injury. The review contains 5 animal tests and 5 clinical studies. Results: Animal tests: CP-98,133 minimized edema, motor damage and is promising in the treatment of memory dysfunction after TBI. The NPS 1506 reduced edema in 24h, without altering the necrosis significantly. Ketamine decreased the volume of necrosis without altering the edema. HU-211 reduced the edema slightly. Clinical studies: NPS 1506 showed a neuroprotective profile and no serius effects. Traxoprodil decreased the mortality rate by 7%. CP-101.606 improved the patient’s condition, without adverse effects. Conclusion: Although NMDA antagonists demonstrate effectiveness in TBI treatment, more studies about adverse effects and efficiency are still needed. Among those analyzed, traxoprodil, NPS-1506 and CP-101.606 still don’t present serious adverse effects and demonstrate effectiveness, proving promising for new studies.