Return of D₄ Dopamine Receptor Antagonists in Drug Discovery

The dopamine D4 receptor garnered a great deal of interest in the early 1990s when studies showed the atypical antipsychotic clozapine possessed higher affinity for D4, relative to other dopamine receptor subtypes, and that this activity might underlie the unique clinical efficacy of clozapine. Unfortunately, D4 antagonists that were developed for schizophrenia failed in the clinic. Thus, D4 fell out of favor as a therapeutic target, and work in...