title: Neuronal nicotinic acetylcholine receptor binding affinities of boron-containing nicotine analogues.
abstract: A series of boron-containing nicotine (NIC) analogues 7-9 was synthesized and evaluated for binding to alpha4beta2 and alpha7 nicotinic receptors. Compound ACME-B inhibited [3H]methyllycaconitine binding to rat brain membranes with a similar potency compared to NIC (Ki = 2.4 and 0.77 microM, respectively), but was markedly less potent in inhibiting [3H]NIC binding when compared to NIC (Ki = 0.60 microM and 1.0 nM, respectively). Thus, tethering a two-carbon bridge between the 2-pyridyl and 3'-pyrrolidino carbons of NIC or 7 affords analogues that bind to the alpha7 receptor in a manner similar to NIC, but with a dramatic loss of affinity for the alpha4beta2 receptor.
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
authors.forename: R
authors.initials: R
authors.lastname: Xu
authors.forename: L P
authors.initials: LP
authors.lastname: Dwoskin
authors.forename: V P
authors.initials: VP
authors.lastname: Grinevich
authors.forename: G
authors.initials: G
authors.lastname: Deaciuc
authors.forename: P A
authors.initials: PA
authors.lastname: Crooks
mesh_terms: D001895:Boron / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D008958:Models, Molecular; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D009538:Nicotine; D001895:Boron