RT Journal Article
T1 Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety
A1 Marco López, Eva María
A1 Rapino, Cinzia
A1 Caprioli, Antonio
A1 Borsini, Franco
A1 Laviola, Giovanni
A1 Maccarrone, Mauro
AB 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.
PB Public Library of Science
SN ESSN: 1932-6203
YR 2015
FD 2015-09-11
LK https://hdl.handle.net/20.500.14352/23303
UL https://hdl.handle.net/20.500.14352/23303
LA eng
NO Ministerio de Ciencia e Innovación (MICINN)
NO Ministero dell’Istruzione, del' Università e della Ricerca (Italia)
NO ALFASIGMA (actual Sigma-Tau)
DS Docta Complutense
RD 30 abr 2024