REVIEW Piracetam's mechanism of action, as with racetams in general, is not fully understood. The drug influences neuronal and vascular functions and influences cognitive function without acting as a sedative or stimulant. Piracetam is a positive allosteric modulator of the AMPA receptor. It is hypothesized to act on ion channels or ion carriers, thus leading to non-specific increased neuron excitability, while explaining its lack of agonistic or inhibitory effect on synaptic action (quite unlike most neurotransmitters), and its low toxicity. GABA brain metabolism and GABA receptors are not affected by piracetam. It has been found to increase blood flow and oxygen consumption in parts of the brain but this may be a side effect of increased brain activity rather than a primary effect or mechanism of action for the drug. Piracetam improves the function of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptors, which are implicated in memory processes. Furthermore, Piracetam may have an effect on NMDA glutamate receptors, which are involved with learning and memory processes. Piracetam is thought to increase cell membrane permeability. Piracetam may exert its global effect on brain neurotransmission via modulation of ion channels (i.e., Na+, K+). It has been found to increase oxygen consumption in the brain, apparently in connection to ATP metabolism, and increases the activity of adenylate kinase in rat brains. Piracetam, while in the brain, appears to increase the synthesis of cytochrome b5, which is a part of the electron transport mechanism in mitochondria. But in the brain, it also increases the permeability of the mitochondria of some intermediaries of the Krebs cycle.
REFERENCES
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Ahmed, A; Oswald, R (2010). Piracetam Defines a New Binding Site for Allosteric Modulators of a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors. J Med. Chem. 53 (5): 2197-2203. doi:10.1021/jm901905j. PMC 2872987. PMID 20163115.
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Gouliaev, AH; Senning, A (1994). Piracetam and other structurally related nootropics. Brain research. Brain research reviews 19 (2): 180-222. doi:10.1016/0165-0173(94)90011-6. PMID 8061686.
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Jordaan, B; Oliver, DW; Dormehl, IC; Hugo, N (1996). Cerebral blood flow effects of piracetam, pentifylline, and nicotinic acid in the baboon model compared with the known effect of acetazolamide. Arzneimittel-Forschung 46 (9): 844-7. PMID 8876930.
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Winnicka, K; Tomasiak, M; Bielawska, A (2005). Piracetam--an old drug with novel properties?. Acta poloniae pharmaceutica 62 (5): 405-9. PMID 16459490.
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