Modelling the binding step in dopamine receptor–antagonist interactions

Abstract

Modelling of the binding step in dopamine receptor–antagonist interactions was undertaken using sixteen antagonists belonging to the following five chemical series: phenothiazines, thioxanthenes, butyrophenones, benzamides, and benzisoxazoles. The Lower Unoccupied Molecular Orbitals (LUMOs) of the antagonists used for these interactions were compared using a similarity τij index, which enabled us to define the characteristic orbital forms of the active molecules. The result of the intersection of these representative orbital forms was the form common to the antagonists' LUMOs. This form corresponds to the orbital form of the indole's Higher Occupied Molecular Orbital (HOMO), and thus suggests that the aromatic binding site of the dopamine receptor is part of a tryptophan type structure.