To summarize recent neuroprotective trials, there has been no useful balance of benefit over risk.1 It is premature to shoot the messenger without evidence either that the results have been misleading or that we have missed trends. Confirmatory trials and/or meta-analysis support the validity of the results, and similar designs have successfully revealed the risks and benefits of thrombolysis. Trial designs have been imperfect, but the message is accurate: the drugs or doses we tried were inadequate. We need safer and better drugs, we need to know when and how to use them, and we need to maximize the efficiency of our trials. All are possible with current designs.2 Originally, limited efficacy data from a single laboratory and an acceptable toxicity profile were sufficient to proceed to clinical development. Choice of dose range, the optimal duration of therapy, patient subgroup selection, and the likely extent of benefit were all reserved for testing in clinical trials. The misplaced optimism of such an approach is now recognized, however, and guidance on preclinical testing has been elaborated.3 Rigorous external scrutiny of preclinical data now occurs in the more informed companies,4 and clinical development is deferred pending resolution of any deficiencies. This is the first role of the (now mandatory) trial steering committee. The drug classes under investigation are evolving, and new approaches are still being discovered. Glutamate antagonists have been widely studied.1 While effective in small animal models, their short time window in the laboratory, failure to protect …