The extracellular entrance provides selectivity to serotonin 5-HT7 receptor antagonists with antidepressant-like behavior in vivo.

Basic Information

ID: ALA3351619

Journal: J Med Chem

Title: The extracellular entrance provides selectivity to serotonin 5-HT7 receptor antagonists with antidepressant-like behavior in vivo.

Authors: Medina RA, Vázquez-Villa H, Gómez-Tamayo JC, Benhamú B, Martín-Fontecha M, de la Fuente T, Caltabiano G, Hedlund PB, Pardo L, López-Rodríguez ML.

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.

CiteXplore: 25073094

DOI: 10.1021/jm500880c

Patent ID: