Antihistaminergics and inverse agonism. Potential therapeutic applications

Autores
Monczor, Federico; Fernández, Natalia Brenda; Fitzsimons, Carlos; Shayo, Carina Claudia; Davio, Carlos Alberto
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The accurate characterization of the molecular mechanisms involved in the action of receptor ligands is important for their appropriate therapeutic use and safety. It is well established that ligands acting at the histamine system currently used in the clinic exert their actions by specifically antagonizing G-protein coupled H1 and H2 receptors. However, most of these ligands, assumed to be neutral antagonists, behave as inverse agonists displaying negative efficacy in experimental systems. This suggests that their therapeutic actions may involve not only receptor blockade, but also the decrease of spontaneous receptor activity. The mechanisms whereby inverse agonists achieve negative efficacy are diverse. Theoretical models predict at least three possible mechanisms, all of which are supported by experimental observations. Depending on the mechanism of action engaged, the inverse agonist could interfere specifically with signaling events triggered by unrelated receptors. This possibility opens up new venues to explain the therapeutic actions of inverse agonists of the histamine receptor and perhaps new therapeutic applications.
Fil: Monczor, Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Fernández, Natalia Brenda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Fitzsimons, Carlos. University Of Amsterdam; Países Bajos
Fil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Davio, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Materia
Histamine receptors
Antihistaminergics
Inverse agonism
Adverse effects
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/6591
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Antihistaminergics and inverse agonism. Potential therapeutic applicationsMonczor, FedericoFernández, Natalia BrendaFitzsimons, CarlosShayo, Carina ClaudiaDavio, Carlos AlbertoHistamine receptorsAntihistaminergicsInverse agonismAdverse effectshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The accurate characterization of the molecular mechanisms involved in the action of receptor ligands is important for their appropriate therapeutic use and safety. It is well established that ligands acting at the histamine system currently used in the clinic exert their actions by specifically antagonizing G-protein coupled H1 and H2 receptors. However, most of these ligands, assumed to be neutral antagonists, behave as inverse agonists displaying negative efficacy in experimental systems. This suggests that their therapeutic actions may involve not only receptor blockade, but also the decrease of spontaneous receptor activity. The mechanisms whereby inverse agonists achieve negative efficacy are diverse. Theoretical models predict at least three possible mechanisms, all of which are supported by experimental observations. Depending on the mechanism of action engaged, the inverse agonist could interfere specifically with signaling events triggered by unrelated receptors. This possibility opens up new venues to explain the therapeutic actions of inverse agonists of the histamine receptor and perhaps new therapeutic applications.Fil: Monczor, Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Fernández, Natalia Brenda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Fitzsimons, Carlos. University Of Amsterdam; Países BajosFil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Davio, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaElsevier2013-09info: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/11336/6591Monczor, Federico; Fernández, Natalia Brenda; Fitzsimons, Carlos; Shayo, Carina Claudia; Davio, Carlos Alberto; Antihistaminergics and inverse agonism. Potential therapeutic applications; Elsevier; European Journal of Pharmacology; 715; 9-2013; 26-320014-2999enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014299913004962info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2013.06.027info:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:12:42Zoai:ri.conicet.gov.ar:11336/6591instacron: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:34982025-10-22 11:12:42.325CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antihistaminergics and inverse agonism. Potential therapeutic applications
title Antihistaminergics and inverse agonism. Potential therapeutic applications
spellingShingle Antihistaminergics and inverse agonism. Potential therapeutic applications
Monczor, Federico
Histamine receptors
Antihistaminergics
Inverse agonism
Adverse effects
title_short Antihistaminergics and inverse agonism. Potential therapeutic applications
title_full Antihistaminergics and inverse agonism. Potential therapeutic applications
title_fullStr Antihistaminergics and inverse agonism. Potential therapeutic applications
title_full_unstemmed Antihistaminergics and inverse agonism. Potential therapeutic applications
title_sort Antihistaminergics and inverse agonism. Potential therapeutic applications
dc.creator.none.fl_str_mv Monczor, Federico
Fernández, Natalia Brenda
Fitzsimons, Carlos
Shayo, Carina Claudia
Davio, Carlos Alberto
author Monczor, Federico
author_facet Monczor, Federico
Fernández, Natalia Brenda
Fitzsimons, Carlos
Shayo, Carina Claudia
Davio, Carlos Alberto
author_role author
author2 Fernández, Natalia Brenda
Fitzsimons, Carlos
Shayo, Carina Claudia
Davio, Carlos Alberto
author2_role author
author
author
author
dc.subject.none.fl_str_mv Histamine receptors
Antihistaminergics
Inverse agonism
Adverse effects
topic Histamine receptors
Antihistaminergics
Inverse agonism
Adverse effects
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The accurate characterization of the molecular mechanisms involved in the action of receptor ligands is important for their appropriate therapeutic use and safety. It is well established that ligands acting at the histamine system currently used in the clinic exert their actions by specifically antagonizing G-protein coupled H1 and H2 receptors. However, most of these ligands, assumed to be neutral antagonists, behave as inverse agonists displaying negative efficacy in experimental systems. This suggests that their therapeutic actions may involve not only receptor blockade, but also the decrease of spontaneous receptor activity. The mechanisms whereby inverse agonists achieve negative efficacy are diverse. Theoretical models predict at least three possible mechanisms, all of which are supported by experimental observations. Depending on the mechanism of action engaged, the inverse agonist could interfere specifically with signaling events triggered by unrelated receptors. This possibility opens up new venues to explain the therapeutic actions of inverse agonists of the histamine receptor and perhaps new therapeutic applications.
Fil: Monczor, Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Fernández, Natalia Brenda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Fitzsimons, Carlos. University Of Amsterdam; Países Bajos
Fil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Davio, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
description The accurate characterization of the molecular mechanisms involved in the action of receptor ligands is important for their appropriate therapeutic use and safety. It is well established that ligands acting at the histamine system currently used in the clinic exert their actions by specifically antagonizing G-protein coupled H1 and H2 receptors. However, most of these ligands, assumed to be neutral antagonists, behave as inverse agonists displaying negative efficacy in experimental systems. This suggests that their therapeutic actions may involve not only receptor blockade, but also the decrease of spontaneous receptor activity. The mechanisms whereby inverse agonists achieve negative efficacy are diverse. Theoretical models predict at least three possible mechanisms, all of which are supported by experimental observations. Depending on the mechanism of action engaged, the inverse agonist could interfere specifically with signaling events triggered by unrelated receptors. This possibility opens up new venues to explain the therapeutic actions of inverse agonists of the histamine receptor and perhaps new therapeutic applications.
publishDate 2013
dc.date.none.fl_str_mv 2013-09
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/11336/6591
Monczor, Federico; Fernández, Natalia Brenda; Fitzsimons, Carlos; Shayo, Carina Claudia; Davio, Carlos Alberto; Antihistaminergics and inverse agonism. Potential therapeutic applications; Elsevier; European Journal of Pharmacology; 715; 9-2013; 26-32
0014-2999
url http://hdl.handle.net/11336/6591
identifier_str_mv Monczor, Federico; Fernández, Natalia Brenda; Fitzsimons, Carlos; Shayo, Carina Claudia; Davio, Carlos Alberto; Antihistaminergics and inverse agonism. Potential therapeutic applications; Elsevier; European Journal of Pharmacology; 715; 9-2013; 26-32
0014-2999
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014299913004962
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2013.06.027
info:eu-repo/semantics/altIdentifier/doi/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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 12.982451

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