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.
Publication types
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Clinical Trial
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Multicenter Study
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Randomized Controlled Trial
MeSH terms
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Adolescent
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Adult
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Aged
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Amygdala / drug effects
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Amygdala / metabolism
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Animals
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Antidepressive Agents, Second-Generation / adverse effects
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Antidepressive Agents, Second-Generation / metabolism
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Antidepressive Agents, Second-Generation / pharmacology
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Antidepressive Agents, Second-Generation / therapeutic use*
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Aprepitant
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Behavior, Animal / drug effects
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Brain / drug effects
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Brain / metabolism
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Depressive Disorder / drug therapy*
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Depressive Disorder / etiology
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Depressive Disorder / metabolism
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Female
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Gerbillinae
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Guinea Pigs
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Humans
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Male
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Middle Aged
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Morpholines / adverse effects
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Morpholines / metabolism
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Morpholines / pharmacology
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Morpholines / therapeutic use*
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Neurokinin-1 Receptor Antagonists*
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Norepinephrine / physiology
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Paroxetine / therapeutic use
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Receptors, Neurokinin-1 / metabolism
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Serotonin / physiology
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Stress, Psychological / drug therapy
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Substance P / antagonists & inhibitors*
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Substance P / metabolism
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Vocalization, Animal / drug effects
Substances
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Antidepressive Agents, Second-Generation
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L 760735
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Morpholines
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Neurokinin-1 Receptor Antagonists
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Receptors, Neurokinin-1
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Aprepitant
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Serotonin
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Substance P
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Paroxetine
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Norepinephrine