Ginkgo BilobavsTianeptine

Ginkgo biloba extract (EGb 761) contains flavonoids (quercetin, kaempferol, isorhamnetin) and terpenoids (ginkgolides A, B, C, J and bilobalide). The flavonoids are potent antioxidants that scavenge superoxide, hydroxyl radicals, and peroxynitrite, and protect neurons from oxidative damage; they may also chelate iron. The terpenoids (ginkgolides and bilobalide) improve blood flow by antagonizing platelet-activating factor (PAF) at the PAF receptor, which reduces platelet aggregation, blood viscosity, and improves microcirculation in the brain. Bilobalide protects mitochondria and reduces apoptosis. Ginkgo modulates nitric oxide (NO) availability via endothelial nitric oxide synthase (eNOS) for vasodilation. It inhibits monoamine oxidase A and B (MAO-A, MAO-B), mildly elevating dopamine and serotonin. It may enhance cholinergic transmission and reduce amyloid aggregation.

Tianeptine is a full agonist at mu-opioid (MOR) and delta-opioid (DOR) receptors, mediating both its antidepressant/anxiolytic effects and abuse potential at high doses. Paradoxically, it enhances serotonin reuptake via SERT—opposite to SSRIs—yet still produces antidepressant effects, possibly through opioid-mediated mood regulation. Tianeptine modulates glutamatergic signaling by reversing stress-induced downregulation of AMPA receptor subunits (GluA1/GluA2) and restoring synaptic plasticity. In the hippocampus and amygdala, it prevents stress-induced dendritic atrophy, spine loss, and CA3 pyramidal cell damage—likely through opioid receptor activation and downstream HPA axis effects. It increases BDNF levels and promotes neurogenesis. The combination of opioid agonism, glutamate normalization, and neuroplasticity enhancement underlies its unique profile.