Galanin Receptor Antagonists as Antidepressants

Science's STKE  06 Dec 2005:
Vol. 2005, Issue 313, pp. tw431
DOI: 10.1126/stke.3132005tw431

The neuropeptide galanin has roles regulating a broad range of processes in the central and peripheral nervous systems, including promotion of anxiety and depression. Swanson et al. used two small-molecule pharmacological inhibitors that selectively inhibit the Gal3 receptor subtype to help define the effects mediated through this receptor in behavioral studies with rodent models of anxiety and depression. They compared the effects of the inhibitors to those of chlordiazepoxide (a benzodiazepine anxiolytic) and fluoxetine (an antidepressant). In several tests, like the social interaction test and the forced swim test, the Gal3 inhibitors showed acute and chronic antidepressant and anxiolytic effects equal to those of the control drugs. The authors propose that Gal3-selective agonists may be useful therapeutics.

C. J. Swanson, T. P. Blackburn, X. Zhang, K. Zheng, Z.-Q. D. Xu, T. Hökfelt, T. D. Wolinsky, M. J. Konkel, H. Chen, H. Zhong, M. W. Walker, D. A. Craig, C. P. G. Gerald, T. A. Branchek, Anxiolytic- and antidepressant-like profiles of the galanin-3 receptor (Gal3) antagonists SNAP 37889 and SNAP 398299. Proc. Natl. Acad. Sci. U.S.A. 102, 17489-17494 (2005). [Abstract] [Full Text]