AniracetamvsSulbutiamine

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.

Sulbutiamine consists of two thiamine (vitamin B1) molecules connected by a disulfide bridge, conferring lipophilicity and efficient blood-brain barrier penetration via passive diffusion. In the brain, it is hydrolyzed to thiamine and increases thiamine diphosphate (TDP) levels—the cofactor for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase, enzymes critical for glucose metabolism and the Krebs cycle. Sulbutiamine upregulates D1 dopamine receptors in the prefrontal cortex, possibly through reduced receptor internalization or increased expression. It modulates glutamatergic transmission (affecting NMDA/AMPA receptor function) and enhances cholinergic transmission. The anti-fatigue and memory-enhancing effects likely stem from improved neuronal glucose oxidation, increased ATP production, and enhanced dopaminergic and cholinergic tone in cognitive circuits.