Distinct Mechanism for Antidepressant Activity by Blockade of Central Substance P Receptors
| Autor: | Angela Williams, Raymond G. Hill, Guanghan Liu, Margaret A. Cascieri, John J. Sramek, John P. Feighner, Gary G. Chicchi, Ram K. Shrivastava, Malcolm MacCoss, Edward M. Scolnick, Duane B. Snavely, Emma J. Carlson, Louise Hewson, Christopher John Swain, Jeffrey J. Hale, Sharon Sadowski, N.R. Cutler, David D. Smith, Nadia M.J. Rupniak, Franz Hefti, Timothy Harrison, Edwina Wyatt-Knowles, Sander G. Mills, Scott A. Reines, Richard Hargreaves, John Carman, Mark S. Kramer |
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| Rok vydání: | 1998 |
| Předmět: |
Adult
Male Serotonin medicine.medical_specialty Adolescent Morpholines Guinea Pigs Substance P Norepinephrine chemistry.chemical_compound Neurokinin-1 Receptor Antagonists Internal medicine Monoaminergic medicine Animals Humans Receptor Aged Depressive Disorder Multidisciplinary Behavior Animal business.industry Antagonist Brain Middle Aged Receptors Neurokinin-1 Amygdala Paroxetine Endocrinology Monoamine neurotransmitter Mechanism of action chemistry Antidepressive Agents Second-Generation Antidepressant Female NK1 receptor antagonist Vocalization Animal medicine.symptom Gerbillinae business Aprepitant Stress Psychological |
| Zdroj: | Science. 281:1640-1645 |
| ISSN: | 1095-9203 0036-8075 |
| DOI: | 10.1126/science.281.5383.1640 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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