AniracetamvsTianeptine

Aniracetam is a positive allosteric modulator of AMPA receptors, binding to the allosteric site and slowing receptor desensitization, which prolongs excitatory postsynaptic currents and facilitates long-term potentiation. It also modulates group II metabotropic glutamate receptors (mGluR2/mGluR3), which regulate presynaptic glutamate release. Uniquely among racetams, aniracetam increases dopamine and serotonin release in the prefrontal cortex via modulation of monoamine transporter activity and vesicular release, contributing to its anxiolytic and mood-enhancing effects. It reduces GABAergic inhibition in the hippocampus through indirect modulation of GABA-A receptors, facilitating NMDA receptor activation and memory consolidation. The lipophilic phenylacetyl group enables rapid blood-brain barrier penetration.

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.