THE DISCOVERY OF POTENT AND SELECTIVE DOPAMINE-D4 RECEPTOR ANTAGONISTS

The identification of a novel dopamine receptor subtype, referred to a s the D4 receptor, which binds the atypical antipsychotic drug clozapi ne with high potency, has led to the initiation of a drug discovery pr ogram that aims to find novel inhibitors of this receptor subtype. A s elective screening strategy was utilized, in which 4500 compounds chos en on the basis of structural similarities to known biogenic amine rec eptor antagonists were tested against both the D4 and D2 dopamine rece ptor subtypes. A potent D4-selective compound was discovered.