Neurokinin 3 (NK3) receptor modulators for the treatment of psychiatric disorders

The neurokinin-3 (NK(3)) is one of the tachykinin peptide neurotransmitter / neuromodulator receptor family. NK(3) receptors are predominantly expressed in neurons of both the peripheral and central nervous systems and in particular, in many of the forebrain areas, such as frontal, parietal and cingulate cortices, and basal ganglia structures implicated in psychiatric disease states. Consistent with this localization pattern, NK(3) receptors appear to modulate monoaminergic and amino acid neurotransmission within these structures. Taken together these observations have lead to the speculation that modulators of NK(3) receptor activity may have therapeutic utility in psychiatric diseases such as schizophrenia and affective disorders. This speculation has recently gained clinical credence through a number of reports of efficacy in placebo controlled studies. In this article, the authors review the recent patent literature highlighting the various NK(3) receptor modulation strategies for potential therapeutic utility in psychiatric disease indications.