Table 1.
Preclinical and clinical studies targeting corticotropin releasing hormone (CRH), arginine vasopressin (AVP), glucocorticoids (GC) or glucocorticoid receptors (GR).
| Context/model | Molecular, cellular & behavioral impacts | Reference | |
|---|---|---|---|
| CRH receptors inhibition | |||
| CRH overexpression | C57/B16 mice | Increase Tau phosphorylation and aggregation. | Campbell et al. (2014) |
| Antalarmin and R121919 (CRH-R1 antagonists) | Aged rats | Prevention of stress-induced memory deficits and anxiety; Prevention of stress-induced synapse loss and HPA axis dysfunction. | Dong et al. (2018) |
| R121919 (CRH-R1 antagonist) | APP/PS1 mice | Prevention of the onset of cognitive impairment; Reduction of cellular and synaptic deficits; Decrease of Aβ and C-terminal fragment levels. | Zhang et al. (2016) |
| NBI 27914 (CRH-R1 antagonist) | PS19 mice | Prevention of stress-induced Tau hyperphosphorylation and aggregation, neurodegeneration and fear memory impairment. | Carroll et al. (2011) |
| Antalarmin (CRH-R1 antagonist) | Tg2576-AD mice | Decrease level of plasma Aβ1–42 and Aβ plaque deposits; Decrease level of plasma corticosterone; Improve memory and anxiety behavior. | Dong et al. (2014) |
| Primary hippocampal culture | Inhibition of Aβ1–42 levels and PKA expression after a CRH treatment. | ||
| AVP receptors inhibition | |||
| SSR149415 (V1b antagonist) | Anxiety/depression rodent models | Anxiolytic-like activity in models involving traumatic stress exposure; Antidepressant-like effects in FST. | Griebel et al. (2002) |
| TASP0390325 and TASP0233278 (VI b antagonists) | Depression rodent models | Antidepressant-like effects in the FST; Reduction of the hyperemotionality after olfactory bulbectomy. | Iijima et al. (2014) |
| ABT-436 (V1b antagonist) | Human (MDD subjects) | Phase 1b in clinical trial for MDD; Reduction of HPA axis hyperactivity; Favorable symptoms changes. | Katz et al. (2017) |
| ABT-436 (V1b antagonist) | Human (alcohol dependence) | Phase 2 in clinical trial for alcohol-dependence; Increase of alcohol abstinence; Reduction of alcohol outcomes for subjects with higher baseline levels of stress. | Ryan et al. (2017) |
| GR modulation | |||
| CORT108297 (sGRm) | 3xTg-AD mice | Reduction of APP C-terminal fragments and p25 levels. | Baglietto-Vargas et al. (2013) |
| Wistar rats | Attenuation of electroconvulsive shock-induced retrograde amnesia. | Andrade et al. (2012) | |
| Sprague–Dawley rats | Reduction of neuroendocrine stress responses and immobility in the FST. | Solomon et al. (2014) | |
| oAβ25–35 rat | Reverse oAβ25–35-induced neuroinflammatory and apoptotic processes, cognitive and synaptic deficits, and APP misprocessing. | Pineau et al. (2016) | |
| CORT113176 (sGRm) | Wobbler mice | Reduction of neurodegeneration and neuroinflammation. | Meyer et al. (2014) |
| oAβ25–35 rat | Reverse oAβ25–35-induced neuroinflammatory and apoptotic processes, cognitive and synaptic deficits, and APP misprocessing. | Pineau et al. (2016) | |
| GC synthesis inhibition | |||
| UE1961 (11β-HSD1 inhibitor) | Aged mice | Improvement of short-term memory. | Sooy et al. (2010) |
| UE2316 (11β-HSD1 inhibitor) | Tg2576-AD mice | Reduction of Aβ plaques in cortex; Increase of IDE levels; Memory improvements. | Sooy et al. (2015) |
| A-918446 (11β-HSD1 inhibitor) | Aged rodents | Improvement of memory consolidation and recall in inhibitory avoidance; Increase of CREB phosphorylation. | Mohler et al. (2011) |
| A-801195 (11β-HSD1 inhibitor) | Improvement of short-term memory | ||
| 11β-HSD1 knock-out | Aged mice | Prevention of intra-neuronal corticosterone increase; Improvement of long term memory (watermaze). | Yau et al. (2001) |
| Metyrapone (1lβ-hydroxylase inhibitor) | SAMP8 mice | Prevention of stress-induced corticosterone elevation, spatial memory deficits and hippocampal neurons loss. | Iinuma et al. (2008) |
| UE2343 (11β-HSD1 inhibitor) | Human | Phase 1 of clinical trial: compound safe, well tolerated and able to penetrate the brain (healthy subjects). | Webster et al. (2017) |
| Carbenoxolone (11β-HSD1 inhibitor) | Aging human | Improvement of verbal memory and fluency. | Sandeep et al. (2004) |