From anesthetic mechanisms research to drug discovery

The ability to render patients insensible and amnesic to remarkably invasive procedures that are uncomfortable to watch, let alone experience, has been rightly designated as one of the greatest medical discoveries of all time. General anesthesia, introduced formally in the mid-nineteenth century, is now delivered to approximately 40 million patients every year in the United States alone. Given its central role in health care, it is indeed extraordinary how poorly we understand anesthesia and anesthetics. In fact, definitions are at best operational and convey little understanding of the underlying neurobiology, while the hypothetical mechanisms are surprisingly superficial. Worse, there is growing concern that the anesthetic drugs in current use, especially the inhaled anesthetics, have durable adverse effects on cognition.