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

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