SYNTHESIS AND IN-VITRO BINDING OF N-ALKYL-2,3-DIMETHOXY-[3.3.1]AZABICYCLONONANE BENZAMIDES AT DOPAMINE D-2 AND D-3 RECEPTORS

A series of N-alkyl analogues of -dimethoxy-N-(9-benzyl)-9-azabicyclo[ 3.3.1]nonan-3 beta-yl benzamide was prepared and their affinity for do pamine D-2 and D-3 receptors was measured in vitro to explore the spat ial 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 D-2 receptor than in the D-3 receptor subtype. These results provide information for the devel opment of pharmacophoric models of the D-2 and D-3 dopamine receptor s ubtypes that can be used for the future development of selective antag onists at these two structurally and pharmacologically similar recepto r subtypes.