Table Box 3.
Potential Antidepressant Pathways and Associated Gene Targets Based on the Predominant Pathways Summarized in Figure 13
| Biochemical pathway | Gene target | Class and example | Target and drug implicated in treating depression? |
|---|---|---|---|
| Neurogenesis | ↑ BDNF | SSRI (fluoxetine, escitalopram) | Yes |
| ↑ TrkB | MAOI (tranylcypramine) | Yes | |
| ↑ VGF | AMPAkines (CX 516;LY 392098); riluzole | Yes | |
| ↑ PKC | mGLUR agonists (LY 404039) | Yes | |
| Excitatory amino acid pathways | ↑ NMDA activity | Glycine and analogs | ? |
| mGLUR1 | Glycine uptake inhibitors | ? | |
| ↑ Vesl/homer | Ampakines (LY 392098); riluzole | Yes | |
| mGLUR antagonists (LY 367385) | Yes | ||
| Cyclic AMP | ↑ cAMP-regulated phosphoprotein | 5-HT1A agonists (buspirone, gepirone) | Yes |
| 5-HT7 agonists (5-CT) | No | ||
| β1 agonists (prenalterol) | No | ||
| ↓ PDE IVB | Selective PDE inhibitors based on rolipram, vipocetine | Yes | |
| Phospholipase/MAP kinase | ↑ PI3 kinase | LY 294002 (antagonist) | ? |
| PD 98059 (antagonist) | ? | ||
| Prostaglandins/arachidonic acid | ↑ cPLA2 | Melitin | Yes |
| ↑ COX2 | Valproate; celecoxib, rofecoxib (antagonists) | Yes | |
| Vascular genesis and remodeling | ↑ VEGF | VEGF, bFGF | Yes |
Validation by drugs used to treat depression is indicated in the last column.