ColuracetamvsOxiracetam

Coluracetam's primary mechanism is enhancement of high-affinity choline uptake (HACU) in hippocampal neurons — the rate-limiting step in acetylcholine synthesis. HACU is mediated by the high-affinity choline transporter (CHT1/SLC5A7), which coluracetam upregulates or potentiates, increasing the Vmax of choline transport into presynaptic terminals. By making this process more efficient, coluracetam increases acetylcholine production and vesicular packaging via the vesicular acetylcholine transporter (VAChT) even when choline levels are normal. This enhances cholinergic transmission in the hippocampus, cortex, and retina — explaining reports of enhanced color vision and visual acuity. Coluracetam also has minor AMPA receptor positive allosteric modulation. The compound was studied for treatment-resistant depression, possibly through cholinergic modulation of mood circuits.

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.