Abstract
Quantitative methods were developed for the determination of dopamine and benzodiazepine receptor characteristics in the living human brain by positron emission tomography (PET). As ligands, the 11C-labelled analogues of the selective antagonists of dopamine receptor subtypes, SCH 23390 and raclopride, and the benzodiazepine antagonist, Ro 15-1788, were used. Tracer amounts of the ligands were injected intravenously into healthy volunteers and schizophrenic patients. The distribution of ligand indicated high densities of D1 as well as D2 dopamine receptors in the basal ganglia. Binding of [11C]-SCH 23390 was also significant in the neocortex where it was shown to represent binding to D1 as well as to 5-HT2 serotonin receptors. High densities of specific benzodiazepine receptor binding were obtained in most neocortical brain areas and in the cerebellum.
Using saturation procedures, B max and K d values could be obtained for D2 and benzodiazepine receptors. A comparison of D2 receptor densities in drug-naive schizophrenic patients and healthy volunteers demonstrated similar receptor characteristics in the major basal ganglia in these groups of subjects. Different chemical classes of conventional and unconventional antipsychotic drugs produced a 65%–85% occupancy of D2 receptors when given in clinical doses to schizophrenic patients. High doses of diazepam produced a marked occupancy of benzodiazepine receptors during the first hours after oral administration to healthy volunteers.
These in vivo methods should be valuable tools for the further analysis of the effects of drug on neuroreceptors in the living brain of neuropsychiatric patients.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Farde L, Ehrin E, Eriksson L, Greitz T, Hall H, Hedström C-G, Litton J-E, Sedvall G (1985) Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography. Proc Natl Acad Sci USA 82: 3863–3867
Farde L, Hall H, Ehrin E, Sedvall G (1986) Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science 231: 258–261
Farde L, Halldin C, Stone-Elander S, Sedvall G (1987 a) PET analysis of human dopamine receptor subtypes using 11C-SCH 23390 and 11C-raclopride. Psychopharmacology (in press)
Farde L, Wiesel F-A, Hall H, Halldin C, Stone-Elander S, Sedvall G (1987 b) PET determination of striatal D2-dopamine receptors in drug-naive schizophrenic patients. Arch Gen Psychiatry 192: 278–284, 1987
Farde L, Wiesel F-A, Hall H, Halldin C, Sedvall G (1987 c) Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Arch Gen Psychiatry 145: 71–76, 1988
Farde L, Pauli S, Hall H, Stone-Elander S, Eriksson L, Halldin C, Hogberg T, Nilsson L, Sjögren I (1987d) Stereoselective binding of 11C-FLB 472 — a search for extrastriatal central D2-dopamine receptors by PET. Psychopharmacology (in press 1988)
Hall H, Farde L, Sedvall G (1987) Human dopamine receptor subtypes — in vitro binding analysis using 3H-SCH 23390 and 3H-raclopride. J Neural Transm (in press)
Persson A, Ehrin E, Eriksson L, Farde L, Hedström C-G, Litton J-E, Mindus P, Sedvall G (1985) Imaging of 11C-labelled Ro 15-1788 binding to benzodiazepine receptors in the human brain by positron emission tomography. J Psychiatr Res 19: 609–622
Sedvall G, Farde L, Persson A, Wiesel F-A (1986) Imaging of neurotransmitter receptors in the living human brain. Arch Gen Psychiatry 43: 995–1005
Wagner HN, Burn HD, Dannals RF, Wong DF, Långström B, Duelfer T, Frost JJ, Ravert HT, Links JM, Rosenbloom SV, Lukas SE, Kramer AV, Kuhar MJ (1983) Imaging dopamine receptors in the human brain by positron tomography. Science 221: 1261–1266
Wong DF, Gjedde A, Wagner HN (1986) Quantification of neuroreceptors in the living human brain. I. Irreversible binding of ligands. J Cereb Blood Flow Metab 6: 147–153
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Sedvall, G., Farde, L., Hall, H., Pauli, S., Persson, A., Wiesel, F.A. (1988). PET Scanning — A New Tool in Clinical Psychopharmacology. In: Casey, D.E., Christensen, A.V. (eds) Psychopharmacology: Current Trends. Psychopharmacology Series, vol 5. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73280-5_3
Download citation
DOI: https://doi.org/10.1007/978-3-642-73280-5_3
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-73282-9
Online ISBN: 978-3-642-73280-5
eBook Packages: Springer Book Archive