Analogues of WAY 100635 as radiotracers for in vivo imaging of 5-HT1A receptors

Abstract

Two diastereoisomeric analogues of the potent 5-HT1A antagonist W A Y 100635 have been synthesized and radiolabelled with 11C; namely trans- and cis-N-[2-[4-(2−methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)-cyclohexanecarboxamide (3 and 4). Both [11C]-3 and [11C]-4 were obtained in modest yields at high specific activities by O-[11C]-alkylation of their respective alkoxide precursors with [11C]-iodomethane. The labelled diastereoisomers were isolated by reverse-phase HPLC and isolated as radiochemically pure formulations for in vivo experiments. Biodistribution studies in rats showed moderate brain uptake for [11C]-4 with little differentiation of uptake between regions rich in 5-HT1A receptors (e.g. hippocampus) and receptor poor regions (e.g. cerebellum). However the diastereoisomeric [11C]-3 possessed better brain uptake with moderate differentiation between 5-HT1A receptor rich and poor regions at early time points (5–30 min post-injection). The results suggest that [11C]-3 may have potential as an in vivo imaging agent for 5-HT1A receptors. Copyright © 1999 John Wiley & Sons, Ltd.