Therapeutic Potential of Tachykinin Receptor Antagonists in Depression and Anxiety Disorders

Abstract

Neuropeptides, including the tachykinins substance P, neurokinin A and neurokinin B, are potentially important new targets for the development of psychotropic drugs. NK1, NK2 and NK3 tachykinin receptor antagonists are currently undergoing clinical trials to investigate their therapeutic applications in central nervous system (CNS) disorders. Substance P (NK1) receptor antagonists (NK1RAs) have been clinically valid ated as a novel approach to treat major depression. Confirmation of the antidepressant efficacy of NK1RAs has been obtained with three separate compounds in double-blind, placebo-controlled clinical trials. NK1RAs are active in a range of preclinical assays that detect clinically used antidepressant and anxiolytic drugs, but they have a profile of activity that is distinct from established drugs. There is preliminary evidence that substance P function may be altered in depressed patients, suggesting a possible link between substance P and depressive pathophysiology. Preclinical studies indicate that the psychotherapeutic effects of NK1RAs may be mediated by direct blockade of NK1 receptors in the amygdala and its associated output projections, through stimulation of hippocampal neurogenesis, and also via interactions with monoamines. Clinical assessment of NK2 and NK3 receptor antagonists in psychiatric disorders is currently in progress.KeywordsSubstance PNK1 receptorNK1 receptorNK3 receptorStressAmygdala