INTRODUCTION: The neurokinin 3 (NK(3)) receptor is a GPCR that has been shown to 
modulate monoaminergic systems within regions of the brain implicated in 
schizophrenia. Preclinical and Phase II clinical results of osanetant and 
talnetant in schizophrenic patients have indicated that NK(3) antagonists may 
provide significant improvement of the positive symptoms and cognitive 
impairment associated with this disorder. Recent findings have also indicated 
that neurokinin B (NKB)-NK(3) signaling plays a key role in the hypothalamic 
regulation of reproduction in humans.
AREAS COVERED: This review article discusses the latest medicinal chemistry 
strategies used to derive novel NK(3) receptor antagonists which have been 
patented during the period 2005 - 2010.
EXPERT OPINION: Since the report of a beneficial effect of osanetant in 
schizophrenic patients, major pharmaceutical companies have been involved in 
this field, leading to a very large number of patent applications disclosed. 
Nevertheless, only three NK(3) selective antagonists entered into Phase II, but 
were then terminated for various reasons. Currently, the main challenge to move 
forward a selective NK(3) antagonist into the clinic would be to define a safety 
margin between the desired therapeutic effect and the effect on testosterone 
levels. The involvement of NKB-NK(3) signaling in reproduction in humans may 
also lead to new exciting indications, such as treatment for sex 
steroid-sensitive cancers of breast and prostate.