title: The extracellular entrance provides selectivity to serotonin 5-HT7 receptor antagonists with antidepressant-like behavior in vivo.
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.
authors: Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense de Madrid , E-28040 Madrid, Spain.
authors: Rocío A
authors: RA
authors: Medina
authors: Henar
authors: H
authors: Vázquez-Villa
authors: José C
authors: JC
authors: Gómez-Tamayo
authors: Bellinda
authors: B
authors: Benhamú
authors: Mar
authors: M
authors: Martín-Fontecha
authors: Tania
authors: T
authors: de la Fuente
authors: Gianluigi
authors: G
authors: Caltabiano
authors: Peter B
authors: PB
authors: Hedlund
authors: Leonardo
authors: L
authors: Pardo
authors: María L
authors: ML
authors: López-Rodríguez
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D005260:Female; D007035:Hypothermia / Q000139:chemically induced; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D056004:Molecular Dynamics Simulation; D009043:Motor Activity / Q000187:drug effects; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C000595017:1-(6-(3,4-dihydroisoquinolin-2(1H)-yl)hex-3-en-1-yl)-1,3-dihydro-2H-indol-2-one; D000928:Antidepressive Agents; D007211:Indoles; D007546:Isoquinolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C104425:serotonin 7 receptor