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

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Marco López, Eva María and Rapino, Cinzia and Caprioli, Antonio and Borsini, Franco and Laviola, Giovanni and Maccarrone, Mauro (2015) Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety. PLoS ONE, 10 (9). ISSN ESSN: 1932-6203

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Official URL: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137034



Abstract

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.


Item Type:Article
Uncontrolled Keywords:Hippocampus; Neostriatum; Drug administration; Frontal lobe; Endocannabinoids; Rodents; Anxiolytics; Peas
Subjects:Medical sciences > Medicine > Pharmacology
Medical sciences > Biology > Animal physiology
Medical sciences > Biology > Neurosciences
ID Code:42484
Deposited On:03 May 2017 15:08
Last Modified:04 May 2017 07:13

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