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Table 5 Studies testing CRHR1 antagonists in mouse models and in vitro models relevant to AD

From: Targeting psychologic stress signaling pathways in Alzheimer’s disease

CRHR1 antagonist Studies Dosage Outcome Comments
Antalarmin Rissman et al. (2012) [59], Dong et al. (2014) [43], Park et al. (2015) [44], 20 mg/kg Rissman (2012) - Able to block acute stress induced tau phosphorylation but not that induced by chronic stress [59]. Dong (2014) - Able to decrease Aβ levels and plaque load in a chronic stress paradigm [43]. Park (2015) - Unable to block rises in Aβ in response to acute stress [44]. Dong (2014) measured PBS soluble Aβ, which represents roughly 5% of total Aβ.
A-helical CRH Park et al. (2015) [44] 5 & 10 μM Unable to block CRH induced Aβ increases in vitro.  
Astressin Park et al. (2015) [44] 5 & 10 μM Unable to block CRH induced Aβ increases in vitro.  
NBI 30775/R121919 Rissman et al. (2012) [59], Campbell et al. (2015) [51], Dong et al. (2014) [43], Zhang et al. (2016) [64] 20 mg/kg. Zhang (2016) utilized osmotic mini pump Campbell (2015) [51] – able to decrease AT8 and PHF-1 phosphorylation in CRH overexpressing mice but not at S262 and S422. Rissman (2012) [59] – Able to decrease stress induced AT8 and PHF-1 increases in phosphorylation  
NBI27914 Park et al. (2015) [44], Lee et al. (2009) [83], Carroll et al. (2011) [54] 10 mg/kg Carroll (2011) [54] - NBI27914 rescued freezing and decreased AT8 phosphorylation and decreased neurodegeneration in PS1 tau transgenic mice.
Lee (2009) [83] – NBI27914 reduced stress induced increases in Aβ levels and plaque load.
Park (2015) [44] – NBI27914 increased secreted Aβ42/ Aβ40 ratio in vitro