All Essential Benefits/Effects/Facts & Information

Pramiracetam is a Racetam molecule that was initially synthesized from Piracetam due to its modifications having more anti-amnesiac potential in rats. Relative to the other racetams, pramiracetam is not that well researched but does appear to have some human evidence.

When looking at the animal evidence, otherwise healthy young and old rats seem to experience benefits to long-term memory formation with supplementation of pramiracetam. It appears to be effective when taken acutely (1-2 hours) before cognitive testing, and studies looking at working memory do not note much effects. Human studies support this, but they are limited in statistical power and currently there are no human studies in otherwise healthy youth for the purpose of cognitive enhancement.

The mechanisms of pramiracetam are not well known, but it appears to alter EEG activity in all tested rats (young and old) and may be able to enhance high-affinity choline uptake. It is similar to piracetam and other racetams in the sense that its mechanisms seem dependent on the adrenal glands and some peripheral effects, but beyond that the mechanisms have not been further elucidated.

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How to Take

Recommended dosage, active amounts, other details

Currently, the evidence using pramiracetam in humans uses either 400mg thrice daily or 600mg twice daily; both of these dosing regiments totals 1,200mg of pramiracetam daily.

It is unsure if pramiracetam should be taken with meals, and it is not clear if 1,200mg is the optimal dosage or not. This does, however, does appear effective.

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Editors' Thoughts on Pramiracetam

Although I have no evidence to support this statement, the fact that pramiracetam is shaped like that structurally (Piraetam plus dipropan-2-aminoethyl) makes me believe that pramiracetam is a prodrug for dipropan-2-aminoethyl that merely gives off piracetam as a byproduct. It does have a bit of structural similarity to choline and pramiracetam has been noted to increase HACU after oral intake but not in vitro, so it is definitely plausible.

Kurtis Frank

Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects pramiracetam has on your body, and how strong these effects are.

Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Forgetting Minor Very High See study
Appears to decrease the influence of amnesiac drugs (scopolamine), and is effective when loaded over a few days rather than relying on acute administration
Cognition Minor Very High See study
Cognitive ability in youth who experienced brain trauma is improved with prolonged usage of pramiracetam, suggesting neuroprotective effects
Memory Minor Very High See 2 studies
While it appears effective in promoting memory formation in elderly persons and cognitively injured youth, there is currently no evidence in otherwise healthy use for nootropic purposes

1Sources and Structure

1.1. Sources

Pramiracetam (full chemical name of Diisoprop-yl-(2-oxopyrrolidin-1-yl)acetamide[1] and codename CI-879[2]) is a synthetic Racetam molecule with structural similarities to the parent molecule, Piracetam, and is used for nootropic purposes albeit in lower dosages. It appears to have been synthesized in 1984 on the basis of being a modification of piracetam that had more anti-amnesiac potential against electrocution.[3]

Pramiracetam is a structural derivative from piracetam that was synthesized on the basis that is conferred more anti-amnesiac properties

1.2. Structure

Pramiracetam is prepared from Piracetam by substituting the amide group with a dipropan-2-ylaminoethyl group,[4] structural information can be read here.[1]


2.1. Serum

Peak plasma concentrations (Cmax) following oral ingestion of pramiracetam in humans are 2.71+/-0.54µg/mL (400mg pramiracetam), 5.40+/-1.34µg/mL (800mg), 6.13+/-0.71µg/mL (1,200mg), and 8.98+/-0.71µg/mL (1,600mg)[5] and elsewhere 600mg has recorded a peak value at 5.80-6.80µg/mL.[6]

The half-life has been noted to be 2.3-3.9 hours in dogs[7] although a human study using a dosage range of 400-1,600mg pramiracetam noted a more prolonged half-life at 4.5-6.5 hours[5] whereas a previous one noted a much more variable half-life of 2-8 hours following 600mg pramiracetam.[6]

Pramiracetam appears to be absorbed in humans and follows linear kinetics in the blood, it has a fairly prolonged yet variable half-life

2.2. Neurological

Pramiracetam has been detected in the brain following oral ingestion to rats[7] but has elsewhere been described as being relatively poorly absorbed across the blood brain barrier.[8]


3.1. Mechanisms

The influence of pramiracetam (0.15-1.5mM) on hippocampal excitatory postsynaptic potentials induced by noted a change of -2.9+/-3.8% from baseline that failed to be significant.[9] Similar to the inefficacy found above, pramiracetam has elsewhere failed to have affinity for dopaminergic, adrenergic, serotoninergic, GABAergic, muscarinic, and adenosinic receptors at an IC50 below 10μM.[10]

No significant per se effects noted on hippocampal cells in vitro

Similar to Piracetam, the memory consolidating effects of pramiracetam can be abolished with an adrenalectomy,[11][12] suggesting a vital role of the adrenal glands. Further studies have noted that aminoglutethimide (prevents conversion of cholesterol to pregnenolone) and epoxymexrenone (aldosterone receptor antagonist) can abolish the effects observed.[11] Elevated corticosteroid levels in general have also been noted to block the effects of these racetam drugs.[13]

Steroid metabolism, namely the aldosterone receptors, appears to be involved in the cognitive enhancing effects of pramiracetam

Pramiracetam has been noted to restore the alterations in EEG function of aged rats to a manner seen in youthful rats noted in the 5-20mg/kg range with efficacy exceeding 200-400mg/kg piracetam.[14] Alterations in brain wave function have been noted in otherwise healthy rats given pramiracetam, and the magnitude of changes in corticol slow waves and hippocampal theta waves correlated with cognitive enhancement in a water maze test.[15]

Pramiracetam appears to influence EEG readings, and this occurs per se in both elderly and young rats. The mechanisms underlying these alterations are not yet known

3.2. Cholinergic Neurotransmission

An intraperitoneal injection of pramiracetam (44-88mg/kg) to rats is able to increase high affinity choline uptake (HACU) in rat hippocampal slices within 30 minutes.[16] This was not seen with piracetam or aniracetam, and both smaller (8.8mg/kg) and larger (176mg/kg) doses were ineffective.[16] Elsewhere, pramiracetam (as well as piracetam) has been noted to normalize the changes induced by scopolamine on choline transport.[17]

When tested in vitro, direct application of pramiracetam to hippocampal slices of naive animals failed to increase HACU.[16]

Pramiracetam may be able to increase high-affinity choline uptake (HACU), the rate-limiting step of acetylcholine synthesis (see the Coluracetam page for more information on HACU)

3.3. Memory and Cognition

The earliest study on the anti-amnesiac potential of pramiracetam reported that the amnesia-reversal potential of pramiracetam with peak efficacy (96% reversal) at 5mg/kg (effective in the range of 12.5-80mg/kg, intraperitoneal injection).[3] This study noted a potency greater than piracetam, which was the basis of synthesizing pramiracetam.[3] Elsewhere, amnesia from the anticholinergic toxin hemicholinium-3 is suppressed with preadministration of pramiracetam.[18]

In regards to amnesiac studies in animals, it has limited evidence but appears to be more potent than piracetam

Exploratory activity appears to be differentially affected by pramiracetam, being increased at 15mg/kg and suppressed at 60mg/kg (30mg/kg had no effect).[19]

In a study assessing the effects of kynurenic acid (Glycine-binding site NMDA agonist) using pramiracetam as a comparator, 30mg/kg pramiracetam was able to enhance object recognition memory.[20] Improvements in object recognition have been noted elsewhere with 30mg/kg pramiracetam (more effective than both 15mg/kg and 60mg/kg) to be comparable to 400mg/kg Piracetam.[19] Step-down avoidance has also noted improvement with oral pramiracetam (100mg/kg) in mice taken 1-2 hours prior to the trial, with comparable efficacy to oxiracetam (same dose) but outperforming piracetam and either performing equally to or outperforming aniracetam.[11][12] Performance in a water maze has been noted to also be improved after a single trial, with 10mg/kg being more effective than lower and higher doses.[15]

Administration (intraperitoneal injections) of pramiracetam at 7.5-15mg/kg to rats over seven weeks of training in a 16-arm radial maze task was able to improve reference (long term) memory without an apparent effect on working memory.[2] While 15mg/kg trended to be more effective than 7.5mg/kg, the difference did not appear to be significant.[2]

Has been confirmed to facilitate long-term memory formation, although no apparent effect on working memory persists. There is efficacy in research animals following acute usage of pramiracetam prior to cognitive testing

In otherwise healthy elderly persons with memory loss, supplementation or pramiracetam over 12 weeks has been noted to improve objective memory retention to a larger degree than memory training (90 minutes weekly with tutors) although the two were additive.[21] Otherwise healthy youth with cerebral injuries paired with memory complaints at a similar dose of pramiracetam (as sulphate; 400mg thrice daily) has noted improvements in memory and cognition, which persisted over 18 months of open label therapy and one month cessation.[22]

In otherwise healthy volunteers given scopolamine after 10 days of pramiracetam supplementation (600mg twice daily) was able to partially reverse the amnesiac effects of scopolamine on episodic memory and selective attention tests.[23]

Although the evidence is fairly limited and in either older subjects or youth with brain injuries, pramiracetam does appear to have nootropic potential after oral ingestion of the standard supplemental dosages in humans

3.4. Alzheimer's Disease

One pilot study using pramiracetam in persons with Alzheimer's disease (particular dose chosen based on what the subject responded to best, in the range of 1,200-4,000mg daily) failed to find any evidence of efficacy and suggested that pramiracetam may not be therapeutic.[24]

Currently no evidence to support the usage of pramiracetam in reducing symptoms or pathology of Alzheimer's disease

4Nutrient-Nutrient Interactions

4.1. Lithium

The ability of pramiracetam to increase nitric oxide synthase (NOS) activity in the cortex of rats, which occurs at 300mg/kg intraperitoneal injections (to 20% higher than baseline) but not 100mg/kg seems to be potentiated with pretreatment with lithium as 100mg/kg pramiracetam can increase NOS to 40% of baseline in this instance.[25]

Scientific Support & Reference Citations


  1. Bambagiotti-Alberti M, et al Diisoprop-yl{2-{2-(2-oxopyrrolidin-1-yl)acetamido}eth-yl}ammonium hydrogen sulfate . Acta Crystallogr Sect E Struct Rep Online. (2008)
  2. Murray CL, Fibiger HC The effect of pramiracetam (CI-879) on the acquisition of a radial arm maze task . Psychopharmacology (Berl). (1986)
  3. Butler DE, et al Amnesia-reversal activity of a series of N-{(disubstituted-amino)alkyl} -2-oxo-1-pyrrolidineacetamides, including pramiracetam . J Med Chem. (1984)
  4. Malykh AG, Sadaie MR Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders . Drugs. (2010)
  5. Chang T, et al Pharmacokinetics of oral pramiracetam in normal volunteers . J Clin Pharmacol. (1985)
  6. Auteri A, et al Pharmacokinetics of pramiracetam in healthy volunteers after oral administration . Int J Clin Pharmacol Res. (1992)
  7. Fang Z, et al Pharmacokinetics of pramiracetam in animals . Hua Xi Yi Ke Da Xue Xue Bao. (1999)
  8. Parnetti L Clinical pharmacokinetics of drugs for Alzheimer's disease . Clin Pharmacokinet. (1995)
  9. Xiao P, et al Selective effects of aniracetam across receptor types and forms of synaptic facilitation in hippocampus . Hippocampus. (1991)
  10. Some neurochemical properties of pramiracetam (CI-879), a new cognition-enhancing agent
  11. Mondadori C, et al Involvement of a steroidal component in the mechanism of action of piracetam-like nootropics . Brain Res. (1990)
  12. Mondadori C, Petschke F Do piracetam-like compounds act centrally via peripheral mechanisms . Brain Res. (1987)
  13. Mondadori C, Ducret T, Häusler A Elevated corticosteroid levels block the memory-improving effects of nootropics and cholinomimetics . Psychopharmacology (Berl). (1992)
  14. Poschel BP, Ho PM, Ninteman FW Arousal deficit shown in aged rat's quantitative EEG and ameliorative action of pramiracetam compared to piracetam . Experientia. (1985)
  15. Poschel BP, et al Pharmacologic therapeutic window of pramiracetam demonstrated in behavior, EEG, and single neuron firing rates . Experientia. (1985)
  16. Shih YH, Pugsley TA The effects of various cognition-enhancing drugs on in vitro rat hippocampal synaptosomal sodium dependent high affinity choline uptake . Life Sci. (1985)
  17. Brust P Reversal of scopolamine-induced alterations of choline transport across the blood-brain barrier by the nootropics piracetam and pramiracetam . Arzneimittelforschung. (1989)
  18. Franklin SR, Sethy VH, Tang AH Amnesia produced by intracerebroventricular injections of hemicholinium-3 in mice was prevented by pretreatment with piracetam-like compounds . Pharmacol Biochem Behav. (1986)
  19. Ennaceur A, et al A new one-trial test for neurobiological studies of memory in rats. II: Effects of piracetam and pramiracetam . Behav Brain Res. (1989)
  20. Hlinák Z, Krejci I Kynurenic acid and 5,7-dichlorokynurenic acids improve social and object recognition in male rats . Psychopharmacology (Berl). (1995)
  21. De Vreese LP, et al Memory training and drug therapy act differently on memory and metamemory functioning: evidence from a pilot study . Arch Gerontol Geriatr. (1996)
  22. McLean A Jr, et al Placebo-controlled study of pramiracetam in young males with memory and cognitive problems resulting from head injury and anoxia . Brain Inj. (1991)
  23. Mauri M, et al Pramiracetam effects on scopolamine-induced amnesia in healthy volunteers . Arch Gerontol Geriatr. (1994)
  24. Claus JJ, et al Nootropic drugs in Alzheimer's disease: symptomatic treatment with pramiracetam . Neurology. (1991)
  25. Corasaniti MT, et al Systemic administration of pramiracetam increases nitric oxide synthase activity in the cerebral cortex of the rat . Funct Neurol. (1995)