Ketamine and neuroprotection. A clinical outlook

As the mechanism of action of ketamine, particularly its non-competitive antagonism at the N-methyl-D-aspartate receptor (NMDA), has become better understood, the use of the drug as a neuroprotective agent has received increasing interest. Although the potential prometabolic effects of ketamine might be counterproductive to neuroprotection, the increase in intracranial pressure it has repeatedly been reported to produce does not appear to be relevant clinically under certain conditions, e.g. in patients with normocapnia and a stable blood pressure. Also, the drug has been shown to be anticonvulsant in clinically applied doses rather than epileptogenic, as was previously assumed. These insights have opened up entirely new perspectives for the use of ketamine as a neuroprotective agent. But as both in vitro and in vivo studies are inconclusive, the benefits of the drug are still controversial. In addition,the potential neurotoxicity attributed to extremely high ketamine doses is poorly understood. Consequently, well controlled animal experiments and studies in humans would be necessary to establish the role of ketamine and its more potent enantiomer S-(+)-ketamine in combination with other neuroprotective measures and to shed lighten its true neuroprotective potential and its possible neuroregenerative effects.