Central nervous system effects of subdissociative doses of (S)-ketamine are related to plasma and brain concentrations measured with positron emission tomography in healthy volunteers

• Published in: Clinical pharmacology and therapeutics Vol. 58; no. 2; p. 165
• Main Authors: Hartvig, P, Valtysson, J, Lindner, K J, Kristensen, J, Karlsten, R, Gustafsson, L L, Persson, J, Svensson, J O, Oye, I, Antoni, G
• Format: Journal Article
• Language: English
• Published: United States 01-08-1995
• Subjects: Adult; Affect - drug effects; Brain - diagnostic imaging; Brain - metabolism; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Ketamine - administration & dosage; Ketamine - blood; Ketamine - pharmacokinetics; Ketamine - pharmacology; Male; Memory - drug effects; Middle Aged; Pain - prevention & control; Reference Values; Tissue Distribution; Tomography, Emission-Computed
• ISSN: 0009-9236
• DOI: 10.1016/0009-9236(95)90194-9

Plasma concentrations, maximum regional brain concentrations, and specific regional binding in the brain after administration of 0, 0.1, and 0.2 mg/kg doses of (S)-ketamine were measured in a randomized, double-blind, crossover study in five volunteers and were related to induced effects such as analgesia, amnesia, and mood changes. Specific binding in the brain was assessed by simultaneous administration of (S)-[N-methyl-11C]ketamine quantified by positron emission tomography. High radioactivities in the brain corresponded to regional distribution of N-methyl-D-aspartate receptor complexes. A significant and dose-dependent reduction of binding was measured as a result of displacement of (S)-[N-methyl-11C]ketamine. Memory impairment and psychotomimetic effects were related to dose, plasma concentration 4 minutes after administration, and decreased regional binding of (S)-ketamine in the brain and were consistently seen at plasma and maximum regional brain (S)-ketamine concentrations higher than 70 and 500 ng/ml, respectively. The magnitude of specific binding of (S)-ketamine, measured with positron emission tomography, can be related directly to drug effects.