Medina, Rocio A.Vázquez Villa, María Del HenarGómez Tamayo, José C.Benhamú Salama, BellindaMartín-Fontecha Corrales, María Del Marde la Fuente, TaniaCaltabiano, GianluigiHedlund, Peter B.Pardo, LeonardoLópez Rodríguez, María Luz2025-01-152025-01-152014-08-14Medina, R. A., Vázquez-Villa, H., Gómez-Tamayo, J. C., Benhamú, B., Martín-Fontecha, M., de la Fuente, T., Caltabiano, G., Hedlund, P. B., Pardo, L., López-Rodríguez, M. L. The Extracellular Entrance Provides Selectivity to Serotonin 5-HT7 Receptor Antagonists with Antidepressant-like Behavior in Vivo. J. Med. Chem. 2014, 57 (15), 6879-68840022-262310.1021/jm500880chttps://hdl.handle.net/20.500.14352/114419The 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal article1520-4804https://doi.org/10.1021/jm500880chttps://pubs.acs.org/doi/10.1021/jm500880crestricted access547GPCRSerotonin 5-HT7 receptorSelective antagonistsMajor depressionAntidepressant-like effectQuímica orgánica (Química)Química farmaceútica2306 Química Orgánica2390.01 Diseño. Síntesis y Estudio Nuevos Fármacos