Synthesis and in vivo evaluation (PIG) of the selective seretonin reuptake inhibitor [11C]NS 2456

Abstract

AbstractWe evaluated a new selective serotonin reuptake inhibitor, NS 2456, to determine whether it is suited for use in PET. Racemic NS 2456 [(1RS, 5SR)‐8‐methyl‐3‐[4‐trifluoromethoxy phenyl]‐8‐azabicyclo [3.2.1]oct‐2‐ene] and its N‐demethylated analogue, racemic NS 2463, selectively inhibit serotonin uptake in rat brain synaptosomes. For uses in PET of the living porcine brain, racemic [11C]NS2463 as well as its radiolabelled enantiomers were used. The compounds crossed the blood‐brain‐barrier rapidly and accumulated preferentially in regions rich in serotonin uptake sites. However their binding potentials were relatively low and no stereoselectivity was found. Thus, neither [11C]NS 2456 nor [11C]‐labelled enantiomers are ideal for PET neuroimaging of neuronal serotonin uptake sites.