(-)-spiro[1-azabicyclo[2.2.2]octane-3,5 '-oxazolidin-2 '-one], a conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the alpha 7 nicotinic acetylcholine receptor

Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the alpha7 nicotinic receptor is a s trong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azab icyclo[2.2.2]octane-3,5'-oxazolidin-2'-one] (4a), a potent full agonist at the rat alpha7 nicotinic receptor, which is highly selective for the rat al pha7 nicotinic receptor over the alpha4 beta2 subtype. Preliminary SAR of A R-R17779 presented here indicate that there is little scope for modificatio n of this rigid molecule as even minor changes result in significant loss o f the alpha7 nicotinic receptor affinity.