Neurokinin(1) receptor antagonists as potential antidepressants

Selective, nonpeptide antagonists for tachykinin receptors first became ava ilable ten years ago. Of the three known tachykinin receptors, drug develop ment has focused most intensively on the substance P-preferring receptor, n eurokinin(1) (NK1). Although originally studied as potential analgesic comp ounds, recent evidence suggests that NK1 receptor antagonists may possess a ntidepressant 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 existi ng 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 N K1 receptor antagonists have served as an impetus for much needed, basic re search in this field.