Bioactive small molecule development- Ketamine metabolite program

National Center For Advancing Translational Sciences

Investigators

Abstract

(R,S)-Ketamine (ketamine) is a dissociative anesthetic that also possesses analgesic and antidepressant activity. Undesirable dissociative side effects and misuse potential limit expanded use of ketamine in several mental health disorders despite promising clinical activity and intensifying medical need. (2R,6R)-Hydroxynorketamine (RR-HNK) is a metabolite of ketamine that lacks anesthetic and dissociative activity but maintains antidepressant and analgesic activity in multiple preclinical models. In a large, collaborative effort we have established the promising preclinical profile of RR-HNK in multiple models of depression and neuropathic and nociceptive pain. We recently completed a Phase 1 study in healthy volunteers (NCT04711005). Which established a safe dose and schedule for this agent and proved that RR-HNK did not possess anesthetic or dissociative characteristics. With several collaborating teams we are currently assessing RR-HNK in multiple Phase 2 studies.