TY - JOUR
T1 - The extracellular entrance provides selectivity to serotonin 5-HT 7 receptor antagonists with antidepressant-like behavior in vivo
AU - Medina, Rocío A.
AU - Vázquez-Villa, Henar
AU - Gómez-Tamayo, José C.
AU - Benhamú, Bellinda
AU - Martín-Fontecha, Mar
AU - De La Fuente, Tania
AU - Caltabiano, Gianluigi
AU - Hedlund, Peter B.
AU - Pardo, Leonardo
AU - López-Rodríguez, María L.
PY - 2014/8/14
Y1 - 2014/8/14
N2 - 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. © 2014 American Chemical Society.
AB - 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. © 2014 American Chemical Society.
U2 - 10.1021/jm500880c
DO - 10.1021/jm500880c
M3 - Article
VL - 57
SP - 6879
EP - 6884
IS - 15
ER -