Ketamine: repurposing and redefining a multifaceted drug

This short review will highlight recent clinical and basic research that supports the therapeutic utility of ketamine as a rapid-acting, life-saving antidepressant and a versatile analgesic. After 50 years of use as a dissociative anesthetic and misuse as a street drug, ketamine has re-emerged as a useful off-label agent for ameliorating various types of pain and resistant depression. In addition to its ability to inhibit N-methyl-d-aspartate (NMDA) receptors, the diverse actions of ketamine might involve epigenetic mechanisms such as microRNA regulation. Thus, ketamine is transitioning from being the pharmacologist's nightmare to one of the most interesting developments in the pharmacology of depression and pain.