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Other names for Pramiracetam
Amacetam, CI-879, N-[2-(Diisopropylamino)ethyl]-2-(2-oxopyrrolidin-1-yl)acetamide, N-[2-(Diisopropylamino)ethyl]-2-oxo-1-pyrrolidineacetamide, N-[2-Bis(1-methyl-ethyl)amino)ethyl]-2-oxo-1-pyrrolidineacetamide, Neupramir, Pramiracetamum, Pramistar (Latvia, Lithuania, Romania), Remen
Pramiracetam Dosage Information
300-600mg taken 1-2 times per day would seem reasonable. Pramiracetam is fat soluble and must be taken with food for maximum absorption. If buying power, please consider that pramiracetam is very bitter and many find it unpleasant.
Pramiracetam was developed in the late 1970s by Parke Davis & Co. (now a subsidiary of Pfizer). The first patent for this drug appeared in 1978 (Belgian) and 1979 (US), concurrent with its first reporting of nootropic characteristics. It is currently classified as a “cognitive enhancer”.
Pramiracetam falls into a class of nootropics called racetams. Racetams are similar, but small structural differences yield a range of different chemical properties. All racetams can pass through the blood-brain barrier at varying degrees, but pramiracetam is the most lipophilic of well-known racetams, thus, is probably absorbed rapidly because of its ability to cross lipid bilayers (though this point was never addressed in any of the literature reviewed, so could be inaccurate). In the table below, more positive log P values reflect higher lipophilicity, whereas more negative log P values reflect higher hydrophilicity.
(Table 2 from )
Some researchers have estimated pramiracetam’s potency to be 5-10x that of the most well-known and well-researched racetam, piracetam. Studies have explored the possibilities of using pramiracetam as a treatment for senile dementia – Alzheimer’s type (SDAT) and concussions. There have been virtually no published papers in the past decade on pramiracetam in animal models and human studies. This lack of interest could be attributed to any of several factors: chance, general disinterest, scientific fads, inefficacy, etc.
Pramiracetam’s Mode of action
As with all members of the racetam family (like piracetam), the specific mechanism of action for pramiracetam is poorly understood. Pramiracetam doesn’t appear to have any affinity for any major neurotransmitter (adenosine, adrenergic, benzodiazepine, dopaminergic, GABAergic, muscarinic, 5-HT/serotonergic) binding sites in rats, meaning this drug doesn’t directly effect changes in neurochemical levels, assuming a reliable animal model.
However, pramiracetam has been linked to a significant increase on the rate of high-affinity choline uptake (HACU) in the rat hippocampus, a part of the brain important for the normal formation of long-term memories. HACU is the primary mechanism by which choline, a critical precursor of acetylcholine, is transported into neurons; HACU is regarded as the rate-limiting step (dictating the rate of the process) for acetylcholine synthesis in neuronal processes. There is a strong correlation between hippocampal acetylcholine activity and the learning and memory-encoding process. An increase in choline uptake (i.e. increased HACU) implies an increase in acetylcholine turnover (synthesis and release), which contributes to increased neuronal septohippocampal neuronal impulse flow. Thus, pramiracetam indirectly increases activity in the hippocampus.
(figure 2 from ; Note: the significant increase in choline uptake in the scopolamine bar represents the cholinergic system’s attempt to overcome scopolamine’s competitive blocking of muscarinic receptors via increased acetylcholine synthesis and release, whereas the significant increase in the pramiracetam bars is a result of pramiracetam’s poorly-understood high-affinity choline uptake-promoting behavior; pramiracetam does not bind to muscarinic receptors, whereas scopolamine does)
Another (non-mutually exclusive from the above) hypothesis is that pramiracetam acts somewhere on a peripheral (non-central/not directly on the brain + spinal cord) site, which relies on the adrenal glands. In a study exploring the relationship between racetams and the adrenal glands in rats, researchers discovered that the significant memory improvements in rats who were administered pramiracetam with adrenal glands intact, were absent in adrenalectomized (adrenal glands removed) rats.
Another (also non-mutually exclusive from the above two) potential mechanism of action is restoration of membrane fluidity. This ‘benefit’ of pramiracetam was vaguely mentioned as a short aside and with little further explanation in a paper exploring racetam-sibling piracetam’s effects on membrane fluidity in aged brains. Increased membrane fluidity facilitates cell signalling.
Generally, researchers have observed pramiracetam to:
- Increase cerebral blood flow,
- Increase cholinergic function and activity (via increased high-affinity choline uptake, or HACU) in the hippocampus,
- Improvements in reference (long-term) memory, in spatial and learning, as can be seen in the figure below, depicting a measurement of reference (long-term) memory in rats placed in a maze,
(Figure 2 from )
- Exhibit neuroprotection towards artificially (scopolamine)-induced amnesia, via HACU, or pumping up acetylcholine synthesis and release.
Whether or not pramiracetam is an effective treatment for cognitive impairment in Alzheimer’s disease patients is debatable. A study with human participants could not find statistically significant improvements in the majority of cognitive tests that its subjects underwent (arguments could potentially be made regarding the small sample size, variation in the AD classification of subjects, a potential performance ‘ceiling’ in the subjects, among maybe other things).
Pramiracetam Dosing (In Depth)
Pramiracetam follows an inverted U-shaped dose response in animal models. In other words, there was a specific mg/kg efficacy range; dosages below and above the boundaries were ineffective. Different studies quoted varying boundaries in animal models:
- Rats – intraperitoneal (i.p.) injection, single time – tested dosages were 8.8 mg/kg, 44 mg/kg, 88 mg/kg and 176 mg/kg; 44 mg/kg and 88 mg/kg were effective, while 8.8 mg/kg and 176 mg/kg were ineffective
- Rats – intraperitoneal (i.p.) injection, single time – tested dosages were 30 mg/kg, 100 mg/kg, 300 mg/kg; 100 mg/kg was the only dosage with significant improvements, whereas 30, and 300 mg/kg produced no significant results
- Rats – intraperitoneal (i.p.) injection, daily injections for 7 weeks – tested dosages were 7.5 mg/kg and 15 mg/kg; both dosages were effective
- Rats – intraperitoneal (i.p.) injection, single time – tested dosage of 100 mg/kg; 100 mg/kg dosage was effective
- Rats – intraperitoneal (i.p.) injection, single time – tested dosages of 15 mg/kg, 30 mg/kg, 60 mg/kg; 15 mg/kg and 30 mg/kg were effective
- Rats – intraperitoneal (i.p.) injection and per oral (p.o.), single time – tested dosage of 100 mg/kg; 100 mg/kg was effective
In summary, i.p. dosages from 7.5 mg/kg to 100 mg/kg, with potentially conflicting boundaries across studies, were found effective in animal models.
In the previously-mentioned study refuting pramiracetam’s effectiveness in treating cognitive deficit in Alzheimer’s disease patients, researchers were unable to find a similar inverted U-shaped dose response for its 10 subjects. Different studies quoted varying boundaries in human models:
- Humans, afflicted with Alzheimer’s disease – inferred per oral (p.o.), daily for 5-8 weeks depending on the subject – tested dosages ranged from 400-4000 mg/day, in an attempt to find each individual’s optimal dose; 1200-3200 mg/day was found to be “optimal” for the individuals in this study, though whether or not the treatment was significantly effective is debatable
- Humans, suffering from brain injuries – inferred per oral (p.o.) – 400 mg doses were given 3 times a day (1200 mg/day)
- Humans, with artificially-induced cognitive impairment, but otherwise healthy – per oral (p.o.), daily for 10 days – 600 mg tablets given 2 times a day (1200 mg/day); study concluded that pramiracetam can protect against the majority of scopolamine’s artificially-induced cognitive impairment
In summary, the p.o. dosage ranged from 1200-3200 mg/day in humans, with 1200 mg/day being most prevalent in the 3 cited studies.
The relationship between pramiracetam’s high lipophilicity and its per oral bioavailability was not addressed in any of the papers reviewed.
The median lethal dosage (LD50) for Pramiracetam is rather high-5434 mg/kg orally for male mice, and 4355 mg/kg orally for female mice. Pramiracetam, like its other racetam siblings, is generally well-tolerated by humans. In a study where participants afflicted with Alzheimer’s disease were treated for 5-8 weeks, symptoms were few and mild: two patients (400-1200 mg/day, per oral) described headaches , and one patient (4000 mg/day, per oral) experienced sleepiness, decreased appetite, and dizziness for 2 days. No adverse events were reported in a study where 24 healthy, male humans were treated with pramiracetam (1200 mg/day, per oral) for 10 days to reduce artificially-induced cognitive impairment.
In a study with healthy, human volunteers, it was found that pramiracetam metabolites were primarily excreted through urine.
In the animal studies reviewed, pramiracetam was mixed with saline and an emulsifier (methylcellulose) to create a suspension, and then injected intraperitoneally. In human studies, pramiracetam was administered orally (capsule or a tablet).
As mentioned earlier, pramiracetam is lipophilic (even more so than its sibling, aniracetam). As lipophilic powders generally do not dissolve in water or water-based liquids (e.g. fruit juice), an emulsifier is required to keep this powder in suspension; alternatively, pramiracetam is also soluble in oil.