Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety

Anxiety disorders are among the most prevalent psychiatric diseases with high personal costs and a remarkable socio-economic burden. However, current treatment of anxiety is far from satisfactory. Novel pharmacological targets have emerged in the recent years, and attention has focused on the endoca...

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Detalles Bibliográficos
Autores: Marco López, Eva María, Rapino, Cinzia, Caprioli, Antonio, Borsini, Franco, Laviola, Giovanni, Maccarrone, Mauro
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/23303
Acceso en línea:https://hdl.handle.net/20.500.14352/23303
Access Level:acceso abierto
Palabra clave:615.9
591.18
Hippocampus
Neostriatum
Drug administration
Frontal lobe
Endocannabinoids
Rodents
Anxiolytics
Peas
Farmacología (Medicina)
Fisiología animal (Biología)
Neurociencias (Biológicas)
2401.13 Fisiología Animal
2490 Neurociencias
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oai_identifier_str oai:docta.ucm.es:20.500.14352/23303
network_acronym_str ES
network_name_str España
repository_id_str
spelling Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of AnxietyMarco López, Eva MaríaRapino, CinziaCaprioli, AntonioBorsini, FrancoLaviola, GiovanniMaccarrone, Mauro615.9591.18HippocampusNeostriatumDrug administrationFrontal lobeEndocannabinoidsRodentsAnxiolyticsPeasFarmacología (Medicina)Fisiología animal (Biología)Neurociencias (Biológicas)2401.13 Fisiología Animal2490 NeurocienciasAnxiety disorders are among the most prevalent psychiatric diseases with high personal costs and a remarkable socio-economic burden. However, current treatment of anxiety is far from satisfactory. Novel pharmacological targets have emerged in the recent years, and attention has focused on the endocannabinoid (eCB) system, given the increasing evidence that supports its central role in emotion, coping with stress and anxiety. In the management of anxiety disorders, drug development strategies have left apart the direct activation of type-1 cannabinoid receptors to indirectly enhance eCB signalling through the inhibition of eCB deactivation, that is, the inhibition of the fatty acid amide hydrolase (FAAH) enzyme. In the present study, we provide evidence for the anxiolytic-like properties of a novel, potent and selective reversible inhibitor of FAAH, ST4070, orally administered to rodents. ST4070 (3 to 30 mg/kg per os) administered to CD1 male mice induced an increase of time spent in the exploration of the open arms of the elevated-plus maze. A partial reduction of anxietyrelated behaviour by ST4070 was also obtained in Wistar male rats, which moderately intensified the time spent in the illuminated compartment of the light-dark box. ST4070 clearly inhibited FAAH activity and augmented the levels of two of its substrates, N-arachidonoylethanolamine (anandamide) and N-palmitoylethanolamine, in anxiety-relevant brain regions. Altogether, ST4070 offers a promising anxiolytic-like profile in preclinical studies, although further studies are warranted to clearly demonstrate its efficacy in the clinic management of anxiety disorders.Public Library of ScienceUniversidad Complutense de Madrid20152015-01-0120152015-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/23303reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/233032026-06-02T12:44:21Z
dc.title.none.fl_str_mv Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety
title Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety
spellingShingle Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety
Marco López, Eva María
615.9
591.18
Hippocampus
Neostriatum
Drug administration
Frontal lobe
Endocannabinoids
Rodents
Anxiolytics
Peas
Farmacología (Medicina)
Fisiología animal (Biología)
Neurociencias (Biológicas)
2401.13 Fisiología Animal
2490 Neurociencias
title_short Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety
title_full Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety
title_fullStr Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety
title_full_unstemmed Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety
title_sort Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety
dc.creator.none.fl_str_mv Marco López, Eva María
Rapino, Cinzia
Caprioli, Antonio
Borsini, Franco
Laviola, Giovanni
Maccarrone, Mauro
author Marco López, Eva María
author_facet Marco López, Eva María
Rapino, Cinzia
Caprioli, Antonio
Borsini, Franco
Laviola, Giovanni
Maccarrone, Mauro
author_role author
author2 Rapino, Cinzia
Caprioli, Antonio
Borsini, Franco
Laviola, Giovanni
Maccarrone, Mauro
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 615.9
591.18
Hippocampus
Neostriatum
Drug administration
Frontal lobe
Endocannabinoids
Rodents
Anxiolytics
Peas
Farmacología (Medicina)
Fisiología animal (Biología)
Neurociencias (Biológicas)
2401.13 Fisiología Animal
2490 Neurociencias
topic 615.9
591.18
Hippocampus
Neostriatum
Drug administration
Frontal lobe
Endocannabinoids
Rodents
Anxiolytics
Peas
Farmacología (Medicina)
Fisiología animal (Biología)
Neurociencias (Biológicas)
2401.13 Fisiología Animal
2490 Neurociencias
description Anxiety disorders are among the most prevalent psychiatric diseases with high personal costs and a remarkable socio-economic burden. However, current treatment of anxiety is far from satisfactory. Novel pharmacological targets have emerged in the recent years, and attention has focused on the endocannabinoid (eCB) system, given the increasing evidence that supports its central role in emotion, coping with stress and anxiety. In the management of anxiety disorders, drug development strategies have left apart the direct activation of type-1 cannabinoid receptors to indirectly enhance eCB signalling through the inhibition of eCB deactivation, that is, the inhibition of the fatty acid amide hydrolase (FAAH) enzyme. In the present study, we provide evidence for the anxiolytic-like properties of a novel, potent and selective reversible inhibitor of FAAH, ST4070, orally administered to rodents. ST4070 (3 to 30 mg/kg per os) administered to CD1 male mice induced an increase of time spent in the exploration of the open arms of the elevated-plus maze. A partial reduction of anxietyrelated behaviour by ST4070 was also obtained in Wistar male rats, which moderately intensified the time spent in the illuminated compartment of the light-dark box. ST4070 clearly inhibited FAAH activity and augmented the levels of two of its substrates, N-arachidonoylethanolamine (anandamide) and N-palmitoylethanolamine, in anxiety-relevant brain regions. Altogether, ST4070 offers a promising anxiolytic-like profile in preclinical studies, although further studies are warranted to clearly demonstrate its efficacy in the clinic management of anxiety disorders.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-01-01
2015
2015-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/23303
url https://hdl.handle.net/20.500.14352/23303
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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