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

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 alpha(4)beta(2) (at the expense of alpha(3)beta(4)) or the alpha(3)beta(4) (at the expense of alpha(4)beta(2)) nicotinic acetylcholine receptor sub-type as compared to the parent compound.