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...
| Authors: | ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2015 |
| Country: | España |
| Institution: | Universidad Complutense de Madrid (UCM) |
| Repository: | Docta Complutense |
| Language: | English |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/23303 |
| Online Access: | https://hdl.handle.net/20.500.14352/23303 |
| Access Level: | Open access |
| Keyword: | 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 |
| _version_ | 1878732033199439872 |
|---|---|
| author | Marco López, Eva María |
| author2 | Rapino, Cinzia Caprioli, Antonio Borsini, Franco Laviola, Giovanni Maccarrone, Mauro |
| author2_role | author author author author author |
| author_browse | Borsini, Franco Caprioli, Antonio Laviola, Giovanni Maccarrone, Mauro Marco López, Eva María Rapino, Cinzia |
| author_facet | Marco López, Eva María Rapino, Cinzia Caprioli, Antonio Borsini, Franco Laviola, Giovanni Maccarrone, Mauro |
| author_role | author |
| collection | Docta Complutense |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_3b85d85aaf23b110aa2e0c19b0124ef5 |
| institution | Universidad Complutense de Madrid (UCM) |
| instname_str | Universidad Complutense de Madrid (UCM) |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:docta.ucm.es:20.500.14352/23303 |
| publishDate | 2015 |
| publishDateSort | 2015 |
| publisher | Public Library of Science |
| publisherStr | Public Library of Science |
| reponame_str | Docta Complutense |
| spelling | Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety Marco López, Eva María Rapino, Cinzia Caprioli, Antonio Borsini, Franco Laviola, Giovanni Maccarrone, Mauro 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 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. Public Library of Science https://hdl.handle.net/20.500.14352/23303 |
| 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 | 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_short | 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 |
| 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 |
| topic_facet | 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 |
| url | https://hdl.handle.net/20.500.14352/23303 |