DMP 696

DMP 696 is a selective corticotropin-releasing hormone receptor 1 (CRHR1) antagonist, used for the treatment of anxiety and depression.

DMP696 (3 mg/kg, p.o.) attenuates consolidation of remote fear memories of mice, without affecting their expression and retention. WT mice treated with DMP696 for 1 week starting 24 h after foot shock also show reduced synaptosomal GluR1 levels than do shocked vehicle-treated controls[1]. Rats treated with different doses of DMP696 (1, 3, 10, 30 mg/kg) show very little freezing during the 2-minute preshock interval. Rats treated with DMP696 exhibit a significant overall reduction in CREB phosphorylation, in both the LA, and BLA, but not in the CeA. DMP696 treatment reduces levels of LA and BLA pCREB across all time intervals that do not differ significantly from homecage pCREB levels (P>0.05). In the CeA, both vehicle- and DMP696-treated rats exhibit significantly higher pCREB expression at each post-conditioning time interval than homecage pCREB levels. Rats in the 30 ng DMP696 group exhibit significantly less freezing in comparison to vehicle-treated animals[2].

[1]. Thoeringer CK, et al. Consolidation of remote fear memories involves Corticotropin-Releasing Hormone (CRH) receptor type 1-mediated enhancement of AMPA receptor GluR1 signaling in the dentate gyrus. Neuropsychopharmacology. 2012 Feb;37(3):787-96. [2]. Hubbard DT, et al. Activation of basolateral amygdala corticotropin-releasing factor 1 receptors modulates the consolidation of contextual fear. Neuroscience. 2007 Dec 19;150(4):818-28. Epub 2007 Oct 5.