Synthesis and in vitro binding of N-alkyl-2,3- dimethoxy[3.3.1]azabicyclononane benzamides at dopamine D₂ and D₃ receptors

A series of N-alkyl analogues of 2,3-dimethoxy-N-(9-benzyl)-9- azabicyclo[3.3.1]nonan-3β-yl benzamide was prepared and their affinity for dopamine D₂ and D₃ receptors was measured in vitro to explore the spatial requirements and relative degree of bulk tolerance in the N-benzyl region of the lead compound. These results suggest a higher degree of bulk tolerance in this binding region of the D₂ receptor than in the D₃ receptor subtype. These results provide information for the development of pharmacophoric models of the D₂ and D₃ dopamine receptor subtypes that can be used for the future development of selective antagonists at these two structurally and pharmacologically similar receptor subtypes.