Ethyl-for-methyl substitution enhances the subtype specificity of mecamylamine analogues

Abstract

The synthesis of novel mecamylamine analogues is described in which one, two or three of the methyl groups of mecamylamine have been systematically replaced with ethyl groups. Assessment of the compounds highlights that simple ethyl for methyl changes changes to the parent structure can dramatically enhance activity and selectivity towards either the α₄β₂ (at the expense of α₃β₄) or the α₃β₄ (at the expense of α₄β₂) nicotinic acetylcholine receptor sub-type as compared to the parent compound.