The Extracellular Entrance Provides Selectivity to Serotonin 5-HT7Receptor Antagonists with Antidepressant-like Behavior in Vivo
- 5 August 2014
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 57 (15) , 6879-6884
Abstract
The finding that ergotamine binds serotonin receptors in a less conserved extended binding pocket close to the extracellular entrance, in addition to the orthosteric site, allowed us to obtain 5-HT7R antagonist 6 endowed with high affinity (Ki = 0.7 nM) and significant 5-HT1AR selectivity (ratio >1428). Compound 6 exhibits in vivo antidepressant-like effect (1 mg/kg, ip) mediated by the 5-HT7R, which reveals its interest as a putative research tool or pharmaceutical in depression disorders.Keywords
Funding Information
- Ministerio de Economía y Competitividad (SAF2010-22198-C02, SAF2013-48271-C2)
- CAM (S2011/BMD2353)
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