Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice

Autores
Berenguer, Inmaculada; Aouad, Noureddine El; Andujar, Sebastian Antonio; Romero, Silvia Vanessa; Suvire, Fernando Daniel; Freret, Thomas; Bermejo, Almudena; Ivorra, María Dolores; Enriz, Ricardo Daniel; Boulouard, Michel; Cabedo, Nuria; Cortes, Diego
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Three series of 1-substituted-7-chloro-6-hydroxy-tetrahydroisoquinolines (1-butyl-, 1-phenyl- and 1-benzyl derivatives) were prepared to explore the influence of each of these groups at the 1-position on the affinity for dopamine receptors. All the compounds displayed affinity for D1-like and/or D2-like dopamine receptors in striatal membranes, and were unable to inhibit [3H]-dopamine uptake in striatal synaptosomes. Different structure requirements have been observed for adequate D1 or D2 affinities. This paper details the synthesis, structural elucidation, dopaminergic binding assays, structure-activity relationships (SAR) of these three series of isoquinolines. Moreover, 1-butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline (1e) with the highest affinity towards D2-like receptors (Ki value of 66 nM) and the highest selectivity (49-fold D2 vs D1) by in vitro binding experiments was then evaluated in behavioral assays (spontaneous activity and forced swimming test) in mice. Compound 1e increased locomotor activity in a large dose range (0.04-25 mg/kg). Furthermore, this lead compound produced reduction in immobility time in the forced swimming test at a dose (0.01 mg/kg) that did not modify locomotor activity. The haloperidol (0.03 mg/kg), a D2 receptor preferred antagonist, blocked the antidepressant-like effect of compound 1e.
Fil: Berenguer, Inmaculada. Universidad de Valencia; España
Fil: Aouad, Noureddine El. Universidad de Valencia; España
Fil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Romero, Silvia Vanessa. Universidad de Valencia; España
Fil: Suvire, Fernando Daniel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Freret, Thomas. Universite de Caen Basse Normandie; Francia
Fil: Bermejo, Almudena. Universidad de Valencia; España
Fil: Ivorra, María Dolores. Universidad de Valencia; España
Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Boulouard, Michel. Universite de Caen Basse Normandie; Francia
Fil: Cabedo, Nuria. Universidad de Valencia; España. Universidad Politécnica de Valencia; España
Fil: Cortes, Diego. Universidad de Valencia; España
Materia
DOPAMINE RECEPTORS
IN VIVO BEHAVIORAL ASSAYS
STRUCTURE-ACTIVITY RELATIONSHIPS
TETRAHYDROISOQUINOLINES
THEORETICAL CALCULATIONS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/127457
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/127457
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in miceBerenguer, InmaculadaAouad, Noureddine ElAndujar, Sebastian AntonioRomero, Silvia VanessaSuvire, Fernando DanielFreret, ThomasBermejo, AlmudenaIvorra, María DoloresEnriz, Ricardo DanielBoulouard, MichelCabedo, NuriaCortes, DiegoDOPAMINE RECEPTORSIN VIVO BEHAVIORAL ASSAYSSTRUCTURE-ACTIVITY RELATIONSHIPSTETRAHYDROISOQUINOLINESTHEORETICAL CALCULATIONShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Three series of 1-substituted-7-chloro-6-hydroxy-tetrahydroisoquinolines (1-butyl-, 1-phenyl- and 1-benzyl derivatives) were prepared to explore the influence of each of these groups at the 1-position on the affinity for dopamine receptors. All the compounds displayed affinity for D1-like and/or D2-like dopamine receptors in striatal membranes, and were unable to inhibit [3H]-dopamine uptake in striatal synaptosomes. Different structure requirements have been observed for adequate D1 or D2 affinities. This paper details the synthesis, structural elucidation, dopaminergic binding assays, structure-activity relationships (SAR) of these three series of isoquinolines. Moreover, 1-butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline (1e) with the highest affinity towards D2-like receptors (Ki value of 66 nM) and the highest selectivity (49-fold D2 vs D1) by in vitro binding experiments was then evaluated in behavioral assays (spontaneous activity and forced swimming test) in mice. Compound 1e increased locomotor activity in a large dose range (0.04-25 mg/kg). Furthermore, this lead compound produced reduction in immobility time in the forced swimming test at a dose (0.01 mg/kg) that did not modify locomotor activity. The haloperidol (0.03 mg/kg), a D2 receptor preferred antagonist, blocked the antidepressant-like effect of compound 1e.Fil: Berenguer, Inmaculada. Universidad de Valencia; EspañaFil: Aouad, Noureddine El. Universidad de Valencia; EspañaFil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Romero, Silvia Vanessa. Universidad de Valencia; EspañaFil: Suvire, Fernando Daniel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Freret, Thomas. Universite de Caen Basse Normandie; FranciaFil: Bermejo, Almudena. Universidad de Valencia; EspañaFil: Ivorra, María Dolores. Universidad de Valencia; EspañaFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Boulouard, Michel. Universite de Caen Basse Normandie; FranciaFil: Cabedo, Nuria. Universidad de Valencia; España. Universidad Politécnica de Valencia; EspañaFil: Cortes, Diego. Universidad de Valencia; EspañaPergamon-Elsevier Science Ltd2009-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/127457Berenguer, Inmaculada; Aouad, Noureddine El; Andujar, Sebastian Antonio; Romero, Silvia Vanessa; Suvire, Fernando Daniel; et al.; Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice; Pergamon-Elsevier Science Ltd; Bioorganic & Medicinal Chemistry; 17; 14; 7-2009; 4968-49800968-0896CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0968089609005598info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bmc.2009.05.079info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:45:31Zoai:ri.conicet.gov.ar:11336/127457instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:45:31.958CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice
title Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice
spellingShingle Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice
Berenguer, Inmaculada
DOPAMINE RECEPTORS
IN VIVO BEHAVIORAL ASSAYS
STRUCTURE-ACTIVITY RELATIONSHIPS
TETRAHYDROISOQUINOLINES
THEORETICAL CALCULATIONS
title_short Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice
title_full Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice
title_fullStr Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice
title_full_unstemmed Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice
title_sort Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice
dc.creator.none.fl_str_mv Berenguer, Inmaculada
Aouad, Noureddine El
Andujar, Sebastian Antonio
Romero, Silvia Vanessa
Suvire, Fernando Daniel
Freret, Thomas
Bermejo, Almudena
Ivorra, María Dolores
Enriz, Ricardo Daniel
Boulouard, Michel
Cabedo, Nuria
Cortes, Diego
author Berenguer, Inmaculada
author_facet Berenguer, Inmaculada
Aouad, Noureddine El
Andujar, Sebastian Antonio
Romero, Silvia Vanessa
Suvire, Fernando Daniel
Freret, Thomas
Bermejo, Almudena
Ivorra, María Dolores
Enriz, Ricardo Daniel
Boulouard, Michel
Cabedo, Nuria
Cortes, Diego
author_role author
author2 Aouad, Noureddine El
Andujar, Sebastian Antonio
Romero, Silvia Vanessa
Suvire, Fernando Daniel
Freret, Thomas
Bermejo, Almudena
Ivorra, María Dolores
Enriz, Ricardo Daniel
Boulouard, Michel
Cabedo, Nuria
Cortes, Diego
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DOPAMINE RECEPTORS
IN VIVO BEHAVIORAL ASSAYS
STRUCTURE-ACTIVITY RELATIONSHIPS
TETRAHYDROISOQUINOLINES
THEORETICAL CALCULATIONS
topic DOPAMINE RECEPTORS
IN VIVO BEHAVIORAL ASSAYS
STRUCTURE-ACTIVITY RELATIONSHIPS
TETRAHYDROISOQUINOLINES
THEORETICAL CALCULATIONS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Three series of 1-substituted-7-chloro-6-hydroxy-tetrahydroisoquinolines (1-butyl-, 1-phenyl- and 1-benzyl derivatives) were prepared to explore the influence of each of these groups at the 1-position on the affinity for dopamine receptors. All the compounds displayed affinity for D1-like and/or D2-like dopamine receptors in striatal membranes, and were unable to inhibit [3H]-dopamine uptake in striatal synaptosomes. Different structure requirements have been observed for adequate D1 or D2 affinities. This paper details the synthesis, structural elucidation, dopaminergic binding assays, structure-activity relationships (SAR) of these three series of isoquinolines. Moreover, 1-butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline (1e) with the highest affinity towards D2-like receptors (Ki value of 66 nM) and the highest selectivity (49-fold D2 vs D1) by in vitro binding experiments was then evaluated in behavioral assays (spontaneous activity and forced swimming test) in mice. Compound 1e increased locomotor activity in a large dose range (0.04-25 mg/kg). Furthermore, this lead compound produced reduction in immobility time in the forced swimming test at a dose (0.01 mg/kg) that did not modify locomotor activity. The haloperidol (0.03 mg/kg), a D2 receptor preferred antagonist, blocked the antidepressant-like effect of compound 1e.
Fil: Berenguer, Inmaculada. Universidad de Valencia; España
Fil: Aouad, Noureddine El. Universidad de Valencia; España
Fil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Romero, Silvia Vanessa. Universidad de Valencia; España
Fil: Suvire, Fernando Daniel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Freret, Thomas. Universite de Caen Basse Normandie; Francia
Fil: Bermejo, Almudena. Universidad de Valencia; España
Fil: Ivorra, María Dolores. Universidad de Valencia; España
Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Boulouard, Michel. Universite de Caen Basse Normandie; Francia
Fil: Cabedo, Nuria. Universidad de Valencia; España. Universidad Politécnica de Valencia; España
Fil: Cortes, Diego. Universidad de Valencia; España
description Three series of 1-substituted-7-chloro-6-hydroxy-tetrahydroisoquinolines (1-butyl-, 1-phenyl- and 1-benzyl derivatives) were prepared to explore the influence of each of these groups at the 1-position on the affinity for dopamine receptors. All the compounds displayed affinity for D1-like and/or D2-like dopamine receptors in striatal membranes, and were unable to inhibit [3H]-dopamine uptake in striatal synaptosomes. Different structure requirements have been observed for adequate D1 or D2 affinities. This paper details the synthesis, structural elucidation, dopaminergic binding assays, structure-activity relationships (SAR) of these three series of isoquinolines. Moreover, 1-butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline (1e) with the highest affinity towards D2-like receptors (Ki value of 66 nM) and the highest selectivity (49-fold D2 vs D1) by in vitro binding experiments was then evaluated in behavioral assays (spontaneous activity and forced swimming test) in mice. Compound 1e increased locomotor activity in a large dose range (0.04-25 mg/kg). Furthermore, this lead compound produced reduction in immobility time in the forced swimming test at a dose (0.01 mg/kg) that did not modify locomotor activity. The haloperidol (0.03 mg/kg), a D2 receptor preferred antagonist, blocked the antidepressant-like effect of compound 1e.
publishDate 2009
dc.date.none.fl_str_mv 2009-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/127457
Berenguer, Inmaculada; Aouad, Noureddine El; Andujar, Sebastian Antonio; Romero, Silvia Vanessa; Suvire, Fernando Daniel; et al.; Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice; Pergamon-Elsevier Science Ltd; Bioorganic & Medicinal Chemistry; 17; 14; 7-2009; 4968-4980
0968-0896
CONICET Digital
CONICET
url http://hdl.handle.net/11336/127457
identifier_str_mv Berenguer, Inmaculada; Aouad, Noureddine El; Andujar, Sebastian Antonio; Romero, Silvia Vanessa; Suvire, Fernando Daniel; et al.; Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice; Pergamon-Elsevier Science Ltd; Bioorganic & Medicinal Chemistry; 17; 14; 7-2009; 4968-4980
0968-0896
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0968089609005598
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bmc.2009.05.079
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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