Research Article

Distinct Mechanism for Antidepressant Activity by Blockade of Central Substance P Receptors

See allHide authors and affiliations

Science  11 Sep 1998:
Vol. 281, Issue 5383, pp. 1640-1645
DOI: 10.1126/science.281.5383.1640

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution


The localization of substance P in brain regions that coordinate stress responses and receive convergent monoaminergic innervation suggested that substance P antagonists might have psychotherapeutic properties. Like clinically used antidepressant and anxiolytic drugs, substance P antagonists suppressed isolation-induced vocalizations in guinea pigs. In a placebo-controlled trial in patients with moderate to severe major depression, robust antidepressant effects of the substance P antagonist MK-869 were consistently observed. In preclinical studies, substance P antagonists did not interact with monoamine systems in the manner seen with established antidepressant drugs. These findings suggest that substance P may play an important role in psychiatric disorders.

  • * To whom correspondence concerning the clinical study should be addressed. E-mail: Mark_Kramer{at}

  • To whom correspondence concerning the preclinical studies should be addressed. E-mail: Nadia_Rupniak{at}

View Full Text

Stay Connected to Science