Neurokinin1 receptor antagonists as potential antidepressants

S. C. Stout, M. J. Owens, C. B. Nemeroff

Research output: Contribution to journalReview articlepeer-review

108 Scopus citations


Selective, nonpeptide antagonists for tachykinin receptors first became available ten years ago. Of the three known tachykinin receptors, drug development has focused most intensively on the substance P-preferring receptor, neurokinin1 (NK1). Although originally studied as potential analgesic compounds, recent evidence suggests that NK1 receptor antagonists may possess antidepressant and anxiolytic properties. If confirmed by further controlled clinical studies, this will represent a mechanism of action distinct from all existing antidepressant agents. As reviewed in this chapter, the existing preclinical and clinical literature is suggestive of, but not conclusive, concerning a role of substance P and NK1 receptors in the pathophysiology of depression and/or anxiety disorders. The ongoing clinical trials with NK1 receptor antagonists have served as an impetus for much needed, basic research in this field.

Original languageEnglish (US)
Pages (from-to)877-906
Number of pages30
JournalAnnual Review of Pharmacology and Toxicology
StatePublished - 2001
Externally publishedYes


  • Antidepressant
  • Anxiolytic
  • MK-869
  • Neuropeptide
  • NK
  • Substance P

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology


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