Publication Date:
1998-09-11
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kramer, M S -- Cutler, N -- Feighner, J -- Shrivastava, R -- Carman, J -- Sramek, J J -- Reines, S A -- Liu, G -- Snavely, D -- Wyatt-Knowles, E -- Hale, J J -- Mills, S G -- MacCoss, M -- Swain, C J -- Harrison, T -- Hill, R G -- Hefti, F -- Scolnick, E M -- Cascieri, M A -- Chicchi, G G -- Sadowski, S -- Williams, A R -- Hewson, L -- Smith, D -- Carlson, E J -- Hargreaves, R J -- Rupniak, N M -- New York, N.Y. -- Science. 1998 Sep 11;281(5383):1640-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Merck Research Laboratories, West Point, PA 19456, USA. Mark_Kramer@merck.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9733503" target="_blank"〉PubMed〈/a〉
Keywords:
Adolescent
;
Adult
;
Aged
;
Amygdala/drug effects/metabolism
;
Animals
;
Antidepressive Agents, Second-Generation/adverse
;
effects/metabolism/pharmacology/*therapeutic use
;
Behavior, Animal/drug effects
;
Brain/drug effects/metabolism
;
Depressive Disorder/*drug therapy/etiology/metabolism
;
Female
;
Gerbillinae
;
Guinea Pigs
;
Humans
;
Male
;
Middle Aged
;
Morpholines/adverse effects/metabolism/pharmacology/*therapeutic use
;
*Neurokinin-1 Receptor Antagonists
;
Norepinephrine/physiology
;
Paroxetine/therapeutic use
;
Receptors, Neurokinin-1/metabolism
;
Serotonin/physiology
;
Stress, Psychological/drug therapy
;
Substance P/*antagonists & inhibitors/metabolism
;
Vocalization, Animal/drug effects
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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