Table 1 Summary of potential targets of antidepressant drugs in relate to AD pathology

Fluoxetine

(SSRI)

Increase synaptic density in hippocampus[75]

Does not interact with Aβ fibrils [159].

Protects hippocampal LTP [100]. Performance improvement in Morris water maze after chronic treatment [102].

Inhibit NMDA receptor directly [127].

Amitriptyline

(NSRI)

Does not increase synapse number but reduce decline in synaptic density [76].

Blocks age --induced deterioration of learning and memory [105].

Tiapentine

(atypical)

Prevents the reduction of dendrites length as a result of chronic stress [77].

Protects hippocampal LTP [99, 100]. No effects on animal performance in Morris water maze[102] but improve animal performance is radial maze discrimination task [104].

TCA

Reduce LTP in CA1 pyramidal cells [96, 97].

Inhibit NMDA receptor directly [124, 125].

Venlafaxine

(SNRI)

Performance improvement in Morris water maze after chronic treatment [101, 103].

Imipramine

(NSRI)

Increase secreted APP, reduces intracellular APP in culture [165].

No effect on animal performance in Morris water maze [101] and even worsen spatial working memory in radial arm maze test [106].

Changes in binding to NMDAR [118, 120]and expression of NMDAR in brain [116]

Citalopram

(SSRI)

Increase the levels of secreted APP in the medium of the treated neurons [165].

Adaptation of NMDAR complex [117]. Changes in expression of NMDAR [116].

Clomipramine (NSRI)

Chronic administration changes the regulation of NMDA receptor control on the release of dopamine [119].

Milnacipran

(NSRI)

Antagonize NMDA receptor uncompetitively [126].

Paroxetine

(SSRI)

Reduces levels of Aβ and tau in Tg mice and cells [157, 161–164]