Thiopental and propofol affect different regions of the brain at similar pharmacologic effects.
Propofol has a greater amnesic effect than thiopental. In this study we tested whether different brain regions were affected by propofol and thiopental at similar drug effects. Changes in regional cerebral blood flow (rCBF) were identified by using SPM99 analysis of images obtained with positron emission tomography with (15)O water. Ten right-handed male volunteers (age, 35 +/- 10 yr; weight, 74.1 +/- 7.5 kg; mean +/- sd) were randomized to receive thiopental (n = 4) or propofol (n = 6) to target sedative and hypnotic concentrations with bispectral index (BIS) monitoring. Four positron emission tomography images were obtained during various tasks at baseline and with sedative and hypnotic effects. Two participants receiving propofol were unresponsive at sedative concentrations and were not included in the final analyses. Median serum concentrations were 1.2 and 2.7 microg/mL for sedative and hypnotic propofol effects, respectively. Similarly, thiopental concentrations were 4.8 and 10.6 microg/mL. BIS decreased similarly in both groups. The pattern of rCBF change was markedly different for propofol and thiopental. Propofol decreased rCBF in the anterior (right-sided during sedation) brain regions, whereas thiopental decreased rCBF primarily in the cerebellar and posterior brain regions. At similar levels of drug effect, propofol and thiopental affect different regions of the brain. These differences may help to identify the loci of action for the nonsedative effects of propofol, such as amnesia.
*Department of Surgical Gastroenterology and †Acute Pain Service, Department of Anesthesiology, Hvidovre University Hospital, Hvidovre, Denmark; ‡Magidom Discovery, LLC, Westport, Connecticut; §Department of Anesthesia, University of Pennsylvania, Philadelphia, Pennsylvania; and ||Purdue Pharma LP, Stamford, Connecticut.
Juri L
JL
Pedersen
Jesper
J
Lillesø
Niels A
NA
Hammer
Mads U
MU
Werner
Kathrine
K
Holte
Peter G
PG
Lacouture
Henrik
H
Kehlet
D000328:Adult; D000339:Affect / Q000187:drug effects; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects*; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006993:Hypnotics and Sedatives; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D015742:Propofol / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D013874:Thiopental / Q000494:pharmacology*; D014055:Tomography, Emission-Computed; D014110:Touch / Q000187:drug effects
D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D002245:Carbon Dioxide; D013874:Thiopental; D010100:Oxygen; D015742:Propofol