Neuronal nicotinic acetylcholine receptor binding affinities of boron-containing nicotine analogues

A series of boron-containing nicotine (NIC) analogues 7-9 was synthesized a nd evaluated for binding to alpha4 beta2 and alpha7 nicotinic receptors. Co mpound ACME-B inhibited [H-3]methyllycaconitine binding to rat brain membra nes with a similar potency compared to NIC (K-i = 2.4 and 0.77 muM, respect ively), but was markedly less potent in inhibiting [H-3]NIC binding when co mpared to NIC (K-i=0.60 muM and 1.0 nM, respectively). Thus, tethering a tw o-carbon bridge between the 2-pyridyl and 3 ' -pyrrolidino carbons of NIC o r 7 affords analogues that bind to the alpha7 receptor in a manner similar to NIC, but with a dramatic loss of affinity for the alpha4 beta2 receptor. (C) 2001 Elsevier Science Ltd. All rights reserved.