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Distinct Mechanism for Antidepressant Activity by Blockade of Central Substance P Receptors
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.
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Metadata
- Authors
- 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. J.
- Venue
- Science
- Published
- 1998-09-11
- Volume
- 281
- Issue
- 5383
- Pages
- 1640-1645
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2140799285
- Cited by
- 1,071
- References
- 1
- FWCI
- 47.76
- Type
- journal article
- Language
- en
- Open access
- closed
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