Selective dopamine D4 receptor antagonists

Abstract

The discovery that the atypical antipsychotic clozapine has higher affinity for the dopamine D₄ receptor relative to the D₂ receptor touched off a search for more potent, highly selective D₄ antagonists as a new class of antipsychotics. Many compounds achieving high potency and selectivity are now available including L-745,870 (Merck), NGD 94-1 (Neurogen), PNU-101,387 (Pharmacia & Upjohn), CP-293,019 (Pfizer), and PD-172,938 (Warner-Lambert). Unfortunately, L-745,870 did not improve psychotic symptoms in a Phase II clinical trial, causing many researchers to question the role of the D₄ receptor in the aetiology of schizophrenia. Recent findings with new biological models and D₄ selective agonists may help clarify D₄ receptor physiology.

• antipsychotic
• CP-226
• 269
• CP-293
• 019
• dopamine D4 antagonist
• L-745
• 870
• NGD 94-1
• NRA0045
• PD-172
• 938
• PD-82
• 011
• PNU-101
• 387
• schizophrenia
• U-99363E
• YM-43611
• YM-50001