Recent advances in neurokinin-3 receptor antagonists

Abstract

This review addresses the recent highlights and progress made in the neurokinin-3 (NK-3) receptor area since the last update, provided in this journal in 1997. Whereas in the neurokinin-1 (NK-1) and neurokinin-2 (NK-2) biological areas literature information based on clinical data account for a high therapeutic potential (in emesis and depression for NK-1 and asthma for NK-2 receptor antagonists), there is a total deficiency of information from NK-3 receptor antagonists in clinical development. No other chemical classes in addition to dichlorophenylalkylpiperidines, represented by SR 142,801 and quinolines, represented by SB-222200 and SB-223412, have been identified by pharmaceutical companies and scientists involved in the specific field. Biological evidence indicates pain/inflammation as a suitable CNS-related therapeutic target, this conclusion is based on localisation studies and efficacy of selected NK-3 receptor antagonists in rat disease models of inflammatory pain. In the periphery, the most likely therapeutic indications might be pulmonary and gastrointestinal tract diseases. It is clearly still premature to anticipate any therapeutic potential in man.

• anxiety
• dichlorophenylalkylpiperidines
• gastrointestinal tract diseases
• inflammation
• neurokinin-3 receptor antagonists
• neurokinin B
• pain
• pulmonary diseases
• quinolines
• SB-222200
• SB-223412
• SR 142,801
• senktide