title: 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.
abstract: 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.
authors.affiliation: Uppsala University PET Centre, University Hospital, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Hartvig
authors.forename: J
authors.initials: J
authors.lastname: Valtysson
authors.forename: K J
authors.initials: KJ
authors.lastname: Lindner
authors.forename: J
authors.initials: J
authors.lastname: Kristensen
authors.forename: R
authors.initials: R
authors.lastname: Karlsten
authors.forename: L L
authors.initials: LL
authors.lastname: Gustafsson
authors.forename: J
authors.initials: J
authors.lastname: Persson
authors.forename: J O
authors.initials: JO
authors.lastname: Svensson
authors.forename: I
authors.initials: I
authors.lastname: Oye
authors.forename: G
authors.initials: G
authors.lastname: Antoni
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D010146:Pain / Q000517:prevention & control; D012016:Reference Values; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D007649:Ketamine