The Nine Lives of Ketamine: From CI-581 to Present Day Clinical Application-Commentary on Domino et al.
Clinical pharmacology and therapeutics – June 01, 2025
Source: PubMed
Summary
From battlefield medicine to breakthrough depression treatment, ketamine's 50-year journey showcases a remarkable evolution in modern medicine. Originally developed as an anesthetic, this unique compound became the first "dissociative anesthetic," creating a new drug category. Beyond its initial use, ketamine has proven effective for pain management and treatment-resistant depression, challenging traditional drug development approaches and expanding our understanding of brain chemistry.
Abstract
The classic article by Domino et al. was the first clinical report and presented the first-in-human study of what would become the drug ketamine. Ketamine has become an analgesic, anesthetic, antidepressant, and drug of misuse. It remains today the only "dissociative anesthetic". It has challenged classical pharmacologic theory and drug development paradigms. The first report on CI-581 could never have envisioned the pharmacologic complexity or clinical utility of this molecule.