AniracetamvsGABA

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.

GABA binds to GABA-A receptors (ligand-gated Cl- channels with alpha1-6, beta1-3, gamma1-3 subunits) and GABA-B receptors (G-protein coupled, Gi/o mediated), reducing neuronal excitability through hyperpolarization. However, supplemental GABA has limited blood-brain barrier penetration due to absence of a dedicated transporter and rapid metabolism by GABA-transaminase and succinate semialdehyde dehydrogenase in periphery. The calming effects may be mediated through: (1) GABA-A and GABA-B receptors in the enteric nervous system (gut-brain axis) — vagal afferents project to the nucleus tractus solitarius and influence limbic regions; (2) small amounts crossing the BBB via paracellular leakage or in individuals with compromised barrier integrity; (3) peripheral effects reducing systemic stress markers (cortisol, heart rate variability). PharmaGABA (Lactobacillus fermentation product) may have better absorption via peptide-like transport or different pharmacokinetics.