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 > 100-fold lower affiinity 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.

Chain-lengthened and imidazoline analogues of nicotine

GIANNELLA, Mario;PIERGENTILI, Alessandro;PIGINI, Maria;QUAGLIA, Wilma;
2000-01-01

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 > 100-fold lower affiinity 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.
2000
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/114415
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