title: Chain-lengthened and imidazoline analogues of nicotine.
abstract: Analogues of nicotine (1) and azanicotine (3) were prepared with an additional methylene group inserted between the two rings (i.e., homonicotine and homoazanicotine; 6 and 5, respectively). Although 6 (Ki = 3110 nM) and 3 (Ki = 206 nM) bind at nACh receptors with > or = 100-fold lower affinity than nicotine (Ki = 2.1 nM), 5 displays high affinity (Ki = 7.8 nM). Like nicotine (ED50 = 12 microg/mouse), both 3 and 5 (ED50 = 21 and 19 microg/mouse, respectively) produced antinociceptive activity in the tail-flick assay following intrathecal administration. The antinociceptive actions of 3 and 5, unlike those of nicotine, were not antagonized by mecamylamine. Compounds 3 and 5 might represent novel analgesic agents that act via a non-nicotinic mechanism, or via a nicotinic mechanism that is distinct from that mediating the antinociceptive actions of nicotine.
authors: Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
authors: G
authors: G
authors: Ferretti
authors: M
authors: M
authors: Dukat
authors: M
authors: M
authors: Giannella
authors: A
authors: A
authors: Piergentili
authors: M
authors: M
authors: Pigini
authors: W
authors: W
authors: Quaglia
authors: M I
authors: MI
authors: Damaj
authors: B R
authors: BR
authors: Martin
authors: R A
authors: RA
authors: Glennon
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D007093:Imidazoles / Q000737:chemistry*; D015394:Molecular Structure; D009538:Nicotine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats
chemical_list: D000700:Analgesics; D007093:Imidazoles; D009538:Nicotine