Uptake and distribution of a new SSRI, NS2381, studied by PET in living porcine brain

• Published in: European neuropsychopharmacology Vol. 9; no. 4; pp. 351 - 359
• Main Authors: Smith, D.F, Gee, A.D, Hansen, S.B, Moldt, P, Østergaard Nielsen, E, Scheel-Krüger, J, Gjedde, A
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.1999
• Subjects: 8-Azabicyclo[3.2.1]oct-2-ene; [ 11C]NS2381; Animals; Biogenic Monoamines - metabolism; Brain - metabolism; Bridged Bicyclo Compounds, Heterocyclic - pharmacokinetics; Citalopram; Living porcine brain; Positron emission tomography; Rats; Serotonin; Serotonin Uptake Inhibitors - pharmacokinetics; SSRI; Stereoisomer; Stereoisomerism; Swine; Tissue Distribution; Tomography, Emission-Computed; SSRI; Stereoisomer; Serotonin; Living porcine brain; Swine; 8-Azabicyclo[3.2.1]oct-2-ene; [ 11C]NS2381; Positron emission tomography; Citalopram
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/S0924-977X(99)00007-3

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. raphé, 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.