Is there still a future for neurokinin 3 receptor antagonists as potential drugs for the treatment of psychiatric diseases?

Selective non-peptide antagonists for the neurokinin 3 (NK3) receptor first became available about twenty years ago. Although the understanding of the role of the NK3 receptor in the brain has been greatly complicated by marked species differences in its distribution and by pharmacological heterogeneity, studies with brain-penetrant non-peptide NK3 receptor antagonists in animals have indicated that these compounds may find utility in a number of psychiatric diseases, including schizophrenia, anxiety and depressive disorders. However, clinical studies with selective NK3 receptor antagonists in these psychiatric conditions have been disappointing and they were unable to confirm the promising therapeutic potential from animal studies, thereby questioning the therapeutic utility of these compounds for CNS disorders. The purpose of this article is to provide a critical overview of the available data on NK3 receptor antagonists in the psychiatry research and development field, by reviewing the behavioral and neurochemical effects of these agents in both preclinical and clinical studies.