Subanesthetic Ketamine Does Not Affect 11C-Flumazenil Binding in Humans

In Brief Positron emission tomography (PET) studies suggest that propofol and inhaled anesthetics increase 11C-flumazenil binding in the living human brain, thus supporting the involvement of γ-aminobutyric acid type A (GABAA) receptors in the mechanism of action of these drugs. Ketamine produces its anesthetic effects primarily by N-methyl-d-aspartate receptor antagonism, but it may also have GABAA receptor agonistic properties. By using PET, we studied the cerebral 11C-flumazenil binding in 10 healthy subjects before and during a subanesthetic racemic ketamine infusion reaching a serum concentration of 350 ± 42 ng/mL. Ketamine did not affect 11C-flumazenil binding to GABAA receptor in the brain, indicating that this mechanism is of minor importance in the actions of subanesthetic ketamine. IMPLICATIONS: Subanesthetic racemic ketamine does not enhance gamma-aminobutyric acid type A receptor binding in the living human brain as assessed with 11C-labeled flumazenil and positron emission tomography.