FasoracetamvsPramiracetam

Fasoracetam upregulates GABA-B receptor (GABA-B1/GABA-B2 heterodimer) expression and function, which is unique among racetams — this receptor upregulation is potentially beneficial for restoring GABAergic sensitivity after prolonged benzodiazepine or phenibut use. It enhances group II metabotropic glutamate receptor (mGluR2/mGluR3) signaling, which modulates presynaptic glutamate release and reduces excitotoxicity. Fasoracetam increases acetylcholine release in the cerebral cortex via modulation of choline acetyltransferase activity and vesicular acetylcholine transporter function. It may also modulate the glutamatergic system through mGluR5. The combination of GABAergic (GABA-B-mediated inhibition), glutamatergic (mGluR modulation), and cholinergic enhancement provides anxiolytic effects alongside cognitive enhancement. Clinical trials focus on ADHD patients with GRM (glutamate receptor) gene variants.

Pramiracetam increases high-affinity choline uptake (HACU) in the hippocampus via potentiation of the choline transporter (CHT1), similar to but 15-30x more potent than coluracetam — dramatically increasing acetylcholine synthesis and release. It modulates AMPA glutamate receptors through positive allosteric modulation, enhancing excitatory neurotransmission. Pramiracetam increases neuronal nitric oxide synthase (nNOS) activity, elevating nitric oxide (NO) production and inducing cerebral vasodilation via cGMP-dependent pathways, thereby enhancing cerebral blood flow and oxygen delivery. The emotional flattening effect suggests significant modulation of prefrontal cortex activity, possibly through excessive cholinergic tone in limbic-prefrontal circuits or reduced dopaminergic/emotional salience signaling. It may also modulate sigma-1 receptor activity.