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 α 4 β 2 (at the expense of α 3 β 4 ) or the α 3 β 4 (at the expense of α 4 β 2 ) nicotinic acetylcholine receptor sub-type as compared to the parent compound. Enhanced activity and selectivity towards either α 3 β 2 or α 2 β 4 nicotinic acetylcholine receptors compared to parent compound.