Hydrophobic group, presence agonists

It seems possible that the presence of a hydrophobic group, such as a phenyl, on the agonist at this location may be one feature which differentiates between an action at DA and DA2 receptors. Two prime examples to consider which seem paradoxical in this context are the l-phenyl-3-benzazepine XVI (SKF 38393) (35) and the 4-phenyl-l,2,3,4-tetrahydroisoquino-lines XVII (36). Both of these possess a phenyl ring which could project into the postulated hydrophobic region of the receptor. However, an analysis of the probable conformations... 

For DA2 receptor agonists, activity may be enhanced by the presence of a hydrophobic binding group at this site. For example, in N-(n-propyl)-N-2-phenethyl substituted compounds, the phenyl ring of the 2-phenethyl substituent could interact with this receptor feature. 

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