TY - JOUR
T1 - Uptake and distribution of a new SSRI, NS2381, studied by PET in living porcine brain
AU - Smith, D. F.
AU - Gee, A. D.
AU - Hansen, S. B.
AU - Moldt, P.
AU - Østergaard Nielsen, E.
AU - Scheel-Krüger, J.
AU - Gjedde, A.
N1 - Funding Information:
We thank the laboratory technicians of the PET Center (Ilse, Vikie, Helle and Gloria), of the HPLC Department at the Psychiatric Hospital in Risskov (Inga, Helle, Kirsten, Nanna and Solvej) and at NeuroSearch (Kathrine, Elsebet, Ulla and Jane) for their skillful assistance. Dr John Hyttel of Lundbeck A/S generously supplied citalopram. The Institute for Experimental Clinical Medicine of Aarhus University provided financial support.
PY - 1999/6/1
Y1 - 1999/6/1
N2 - This study tests the utility of a new selective serotonin reuptake inhibitor (SSRI), [11C]NS2381 {(±)-(8-[11C]methyl-3-(4-trifluoromethyl-phenyl)-8-azabicyclo[3.2.1]oct-2-ene)}, as positron-emitting radioligand for labelling serotonin (5-HT) reuptake sites in living brain. Studies of monoamine uptake were carried out initially in vitro using rat brain synaptosomes. They showed that NS2381 and its precursor NS2435 are selective inhibitors of serotonin (5-HT) uptake. Then, studies were carried out in vivo on the uptake and distribution of [11C]NS2381 in living porcine brain. They showed that the radiotracer accumulates readily in brain, and binds reversibly in regions rich in serotonin uptake sites (e.g. raphe, basal ganglia and thalamus). In addition, [11C]NS2381 was displaced from brain tissue by the potent SSRI citalopram. The enantiomers of [11C]NS2381 were, in general, found to be similar to the racemate in terms of their uptake and distribution in living pig brain. Thus, [11C]NS2381 fulfilled several criteria of a PET radioligand for studying 5-HT uptake sites in the living brain. Copyright (C) 1999 Elsevier Science B.V./ECNP.
AB - This study tests the utility of a new selective serotonin reuptake inhibitor (SSRI), [11C]NS2381 {(±)-(8-[11C]methyl-3-(4-trifluoromethyl-phenyl)-8-azabicyclo[3.2.1]oct-2-ene)}, as positron-emitting radioligand for labelling serotonin (5-HT) reuptake sites in living brain. Studies of monoamine uptake were carried out initially in vitro using rat brain synaptosomes. They showed that NS2381 and its precursor NS2435 are selective inhibitors of serotonin (5-HT) uptake. Then, studies were carried out in vivo on the uptake and distribution of [11C]NS2381 in living porcine brain. They showed that the radiotracer accumulates readily in brain, and binds reversibly in regions rich in serotonin uptake sites (e.g. raphe, basal ganglia and thalamus). In addition, [11C]NS2381 was displaced from brain tissue by the potent SSRI citalopram. The enantiomers of [11C]NS2381 were, in general, found to be similar to the racemate in terms of their uptake and distribution in living pig brain. Thus, [11C]NS2381 fulfilled several criteria of a PET radioligand for studying 5-HT uptake sites in the living brain. Copyright (C) 1999 Elsevier Science B.V./ECNP.
KW - 8-Azabicyclo[3.2.1]oct-2-ene
KW - Citalopram
KW - Living porcine brain
KW - Positron emission tomography
KW - SSRI
KW - Serotonin
KW - Stereoisomer
KW - Swine
KW - [C]NS2381
UR - http://www.scopus.com/inward/record.url?scp=0033153225&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033153225&partnerID=8YFLogxK
U2 - 10.1016/S0924-977X(99)00007-3
DO - 10.1016/S0924-977X(99)00007-3
M3 - Article
C2 - 10422897
AN - SCOPUS:0033153225
SN - 0924-977X
VL - 9
SP - 351
EP - 359
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 4
ER -