Piracetam

olinks: Racetams Nootropics reference:

• https://raypeatforum.com/community/threads/piracetam-study-depository.42363/ 4-13-2021

Piracetam #

Some of this stuff may be applied to all racetams. Gotta find the commonalities.

• Crosses the BBB and is found in all tissue.
• https://men-elite.com/2020/12/04/the-dopamine-dream-team-stack-try-this-for-laser-sharp-focus-and-euphoria/ (some of these I had already written down from other sources)
• Decreases the destabilizing effects Amyloid β, which causes lipid disorganization within cell membranes. Other racetams do this as well.
  • Increases (synthesis of) cytochrome B5
  • Inhibits stress-induced Prolactin increase
• Reduces Erythrocyte adhesion to vascular endothelium, hinders vasospasm, and facilitates microcirculation. R
• GABA transaminase inhibition.
• Influences Membrane fluidity in the whole body; protecting the cell against Hypoxia. That shit’s crazy
• Increases brain O2 consumption, in connection to ATP metabolism.
• Piracetam Defines a New Binding Site for Allosteric Modulators of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors (Ahmed & Oswald 2010)
  • GluR2/GluR3.
  • Along with Aniracetam, Both drugs bind to GluA2 and GluA3 in a very similar manner, suggesting little subunit specificity.
  • Piracetam binds to multiple sites along the dimer interface with low occupation, one of which is a unique binding site for potential allosteric modulators.
  • However, the binding sites for piracetam and Aniracetam differ considerably.

• Aldosterone receptors are involved in the mediation of the memory-enhancing effects of piracetam
  • Adrenalectomy blocks memory-enhancing effects of piracetam. This is abolished with administration of corticosterone or aldosterone so long as aldosterone receptors (Type I mineralcorticoid receptor) are not blocked.
• Blockade of the nootropic action of piracetam-like nootropics by adrenalectomy: an effect of dosage?
• Involvement of a steroidal component in the mechanism of action of piracetam-like nootropics

Neurotransmission #

• Derivative of GABA. Indeed it appears to potentiate GABA
• Increases Dopamine in cerebral cortex and striatum, and Serotonin in the cortex, while reducing serotonin in the Striatum, Brain Stem and Hypothalamus. R
• Increases Noradrenaline by increasing Locus Coeruleus firing. R
• Increases Noradrenaline and Serotonin turnover in Hippocampus.

Choline #

• Acetylcholinesterase inhibitor, in contrast to some other racetams that increase its synthesis.
• Increases hippocampal acetylcholine, and in aged mice, increases population of mAChR in frontal cortex by up to 40%.
  • Carbachol-induced accumulation of Inositol Monophosphates was elevated, suggesting piracetam can normalize functional deficits associated with aging
• Profound effects of combining choline and piracetam on memory enhancement and cholinergic function in aged rats
  • 200mg/kg increased Choline content in Hippocampus by 88%, and decreased Acetylcholine levels by 19%.
  • Choline administration raised choline content about 50% in the Striatum and Cerebral Cortex, and 6-10% increase in ACh levels. None in hippocampus.
    • The combination of choline and piracetam did not potentiate these effects seen with either drug alone, and in some cases, were worse.
  • Rats given 100mg/kg of piracetam+choline exhibited retention scores several times better than piracetam alone. 200mg/kg of choline or piracetam alone was still inferior.

Glutamate #

• Enhances efficacy of AMPA-induced calcium influx and maximal density of AMPARs in synaptic membranes, due to the recruitment of a subset of AMPA receptors which normally don’t contribute to synaptic transmission.
  • Normalized the age-related elevated affinity of L-glutamate for NMDAR
• Binds to AMPARs with much lower affinity than ampakines or Aniracetam, but it can bind to multiple sites on the AMPA receptor, potentiating what binds to it, including piracetam itself.
• Larger doses can potentiate potassium-induced release of glutamate from hippocampal nerves.
• Significantly increases NMDAR density by 20% after 14 days of treatment.
• Allosteric modulator of certain CNS glutaminergic receptors. I wanna know how this prevents overactivation, because it does.

Supplementation #

• 4-5 hour half life (peak @ 30 minutes after; maybe 2 hours) after oral administration. 8.5 hour half life in cerebrospinal fluid.
• Supposedly near-100% oral bioavailability.

Dosage #

Piracetam is virtually nontoxic, but are high doses a waste of money?

• Effect of piracetam, a nootropic agent, on rat brain monoamines and prostaglandins
  • 20mg/kg (1.5g) and 100mg/kg (7.5g): The former decreased Serotonin levels and increased Noradrenaline and Dopamine, while the higher dose had the opposite effect. The lower dose produced a statistically insignificant increase in PGE2 and PGF2α, and the higher dose markedly increased both.
• 9.6-20g/day for 18-26 months; n=11, well tolerated in treatment of myoclonus with the addition of various pharmeceuticals. R
• 8g/day for 1 year, and the drug was well tolerated in patients with early probable Alzheimer’s. R
• http://www.longecity.org/forum/topic/54322-piracetam-dosage-why-you-should-be-taking-48-grams-dose/
  • 9.6/day is $40 per 26 days for ND.
  • The greatest therapeutic benefits occured at 9.6 grams, with this total being split 2-3 times.
    • This might just be due to acute effects - you can maybe taper it down. But some of these studies were conducted for weeks.
  • These effects are greatest between 1 (peak plasma concentrations when fasting) and 4 h after dosage, and then diminish progressively to disappear between 8 and 12 h after administration.
  • These conclusions are not exactly absolute. A lot of people like 1.6 instead, or begin to experience lethargy, etc. with 4.8. People even experience benefits from microdoses, like 60mg; probably sublingual.
  • “interestingly enough, the outer layers of the cortex which assist in language recall may be less saturated in M1 and M2 sites than the more evolved, highly saturated frontal lobe which controls moreso mood and higher order cognitive functions. then what happens at high does of piracetam is the language centers and outer cortex are attuned just right (as is often reported in the literature) while the frontal lobe experiences a tremendous and overwhellming surge in cholinergic activity. so it short-circuits with the accompanying brain fog and low mood and suddenly you’re in no shape to take a university exam. but somehow amidst everything your verbal fluency is still on point”