AniracetamvsOxiracetam

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.

Oxiracetam enhances glutamatergic neurotransmission through positive allosteric modulation of AMPA receptors, increasing the amplitude and duration of excitatory postsynaptic potentials. It increases the release of excitatory neurotransmitters glutamate and D-aspartic acid from hippocampal presynaptic terminals, acting as a glutamate analog. Oxiracetam stimulates protein kinase C (PKC) isoforms, particularly PKC-α and PKC-γ, which phosphorylate substrates involved in memory consolidation, long-term potentiation (LTP), and synaptic plasticity. PKC activation enhances NMDA receptor function and AMPA receptor trafficking to the synapse. Its mild stimulatory effect derives from cholinergic system enhancement via increased acetylcholine release and nicotinic α7 receptor potentiation in the cortex.