NK1 receptor antagonists under investigation for the treatment of affective disorders

Substance P-neurokinin-1 (NK1) receptor pathways have been repeatedly implicated in the pathophysiology of affective disorders. Anatomical studies in humans have shown a high expression of NK1 receptors in brain regions that are important for the regulation of affective behaviours and stress responses. A large body of evidence that has been generated from animal experiments indicates that treatment with a selective NK1 receptor antagonist might be effective in the treatment of certain forms of anxiety and depressive disorders. Accordingly, numerous NK1 receptor antagonists have either been synthesised and are under clinical development, or have already been tested in clinical trials. However, the initial encouraging clinical results were followed by repeated demonstrations of a lack of effectiveness, thus disappointment and doubt currently surrounds the idea that these compounds may become effective antidepressants. Research continues and novel molecules may show better pharmacokinetic and pharmacodynamic properties and, therefore, may achieve therapeutic success. Furthermore, NK1 receptor antagonists that are ineffective in the treatment of mood disorders may still prove to be effective in the treatment of anxiety problems.