Distinct Mechanism for Antidepressant Activity by Blockade of Central Substance P Receptors-Reference-Cited by-同舟云学术

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

Published:1998-09-11 Issue:5383 Volume:281 Page:1640-1645
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Kramer Mark S.¹²,Cutler Neal¹²,Feighner John¹²,Shrivastava Ram¹²,Carman John¹²,Sramek John J.¹²,Reines Scott A.¹²,Liu Guanghan¹²,Snavely Duane¹²,Wyatt-Knowles Edwina¹²,Hale Jeffrey J.¹²,Mills Sander G.¹²,MacCoss Malcolm¹²,Swain Christopher J.¹²,Harrison Timothy¹²,Hill Raymond G.¹²,Hefti Franz¹²,Scolnick Edward M.¹²,Cascieri Margaret A.¹²,Chicchi Gary G.¹²,Sadowski Sharon¹²,Williams Angela R.¹²,Hewson Louise¹²,Smith David¹²,Carlson Emma J.¹²,Hargreaves Richard J.¹²,Rupniak Nadia M. J.¹²

Affiliation:

1. M. S. Kramer is at Merck Research Laboratories, West Point, PA 19456, USA, and in the Department of Psychiatry and Human Behavior, Thomas Jefferson Medical College, Philadelphia, PA 19107, USA. N. Cutler and J. J. Sramek are at California Clinical Trials, Beverly Hills, CA 90211, USA. J. Feighner is at the Feighner Research Institute, San Diego, CA 92121, USA. R. Shrivastava is at the Eastside Medical Group, New York, NY 10021, USA. J. Carman is at Carman Research, Smyrna, GA 30080, USA. S. A....

2. M. Kramer and N. Rupniak are the principal contributors to the clinical and preclinical studies, respectively.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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