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The Nine Lives of Ketamine: From CI-581 to Present Day Clinical Application-Commentary on Domino et al.

Evan D Kharasch

Clinical pharmacology and therapeutics June 1, 2025 DOI: 10.1002/cpt.3634 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics First-in-human study Peer reviewed
Population Human
Topics Esketamine Ketamine
Keywords Anesthesia Psychopharmacology Mental health Drug development
Citations 4
Key points The first clinical report of ketamine (then CI-581) introduced a drug that would become a dissociative anesthetic with multiple uses, challenging classical pharmacology and drug development.

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.