As stated in my previous article, racetams were the original smart drugs and were dubbed “nootropics,” meaning towards the mind. Continuing with the racetam family, I would like to discuss a few others that show promise in mental acuity and focus, as a replacement for amphetamines.
Another favorite racetam of mine is oxiracetam. Comparing the structures below, you can see that ociracetam only differs from piracetam by the addition of a hydroxyl (alcohol) group on carbon 4 of the 2-pyrrolidone backbone.
Related - Racetams - The Original Smart Drugs
This addition makes the molecule less lipophilic than piracetam, however it can be used in lower doses. Piracetam can actually cross the blood-brain barrier slightly better than oxiracetm (5.3% vs 5.5%, respectively). This suggests that oxiracetam’s addition of the hydroxyl group affects pharmacodynamics (receptor affinity) rather than pharmacokinetics (getting into your brain).
More on Oxiracetam
Oxiracetam is thought to work as an AMPA receptor modulator, but differing slight from the other racetams. It seems to bind to a different site on the receptor, suggesting that oxiracetam can be co-ingested with other racetms for an additive effect, and not competing for the same binding pocket.
Oxiracetam also seems to facilitate the release of not only glutamate, like most racetams, but also D-aspartic acid and interacts with Protein Kinase C (PKC), which may explain its memory promoting/enhancing effects. 
Oxiracetam has been shown reduce the cognitive decline in subjects with Alzheimer’s disease, dementia, as well as other degenerative brain conditions. Most of these studies were in elderly populations in a diseased state, with average doses between 400-1600mg daily. The most noticeable effects were improvements include verbal learning and quality of life. 
Unlike other racetams, oxiertam has been shown to have a cholinergic effect, preventing the reduction in levels acethylcholine, as well as enhancing the enzyme acetylcholinetrasnferase (responsible for synthesizing aceylcholine.  The cholinergic effect has also been noted to have a memory-enhancing effect, as well as being psychostimulatory, but to a much lesser extent than other psychostimulants like amphetmaine. 
Also worth mentioning, repeated daily doses of oxiracetam was shown to increase utilization of acetylcholine by 31% compared to the placebo, and works better than piracetam.  Unfortunately, there have not been any studies with oxiracetam in young, healthy subjects. Typical doses of oxiracetam are 800mg-1600mg, 2 times daily, as it has a half-life of approximately 8 hours.
Coluracetam - Racetam and Nootropic
The last racetam I'm going to discuss differs from all the racetams previously mentioned in these articles.
Coluracetam is classified as a racetam and nootropic, but looking the chemical structures, one can see they are quite different. While it does contain the 2-prroylidone backbone, it also contains a very bulky tricyclic sidechain which drastically changes its mechanism of action. First synthesized in 1993 in Japan, it was designed to be a choline uptake enhancer that can selectively affect memories. 
Coluracetam is a much different mechanism of action compared to most racetams. It is known as a high affinity choline uptake (HACU) enhancer, which means that it facilitates the uptake of choline into a neuron for synthesis of acetylcholine, which is the rate-limiting step for acetylcholine syntheis. This is most likely the reason for its cognitive enhancement. 
This mases coluracetam a promising drug for Alzheimer’s disease.
As far as studies go, almost all studies involving colureactam are in the prescence of AF64-A, a known cholinergic toxin that decreases levels of acetylcholine. This makes it very difficult to access if coluracetam can be beneficial on its own.
Coluracetam does seem to have a positive effect on CHT1, a choline transporter, but mostly in toxin-induced impaired HACU. It should be noted that the memory-enhancing effects build up over time, and are not immediate.
However, worth mentioning that in the rat study where they were given the cholinergic toxin AF64-A concurrently with 3mg of coluracetam, the rats seemed to experience the memory-enhancing effects for up to 3 days after their last dose. Whether this translates to humans is unclear at this time.
Coluracetam as a very short half-life, approximately one hour, and most be dosed frequently throughout the day. Common doses are between anywhere from 3-35mg 3x a day. It is also recommended that since it can improve the uptake of choline in to neurons for the synthesis of acetylcholine, that one should concurrently supplement with a choline source such as alpha-GPC or CDP-choline.
Doses for those compounds are 300-600mg/d and 250-1000mg/d, respectively.
My final thoughts on racetams.
I have a huge fan of the use of racetams for focus and mental aquity, and often will use them in place of caffeine. I typically will take 800mg of oxiracetam, 150mg of phenylpiractam, along with 1000mg of CDP-choline first thing in the morning to get my brain going.
Racetams have an excellent safety record and can be very beneficial for individuals looking for clean focus without the jitters of caffeine or amphetamine-like stimulants.
In the next installment of this article, I will talk about the different choline sources available, and possibly dive into the prescription medications people often use for concentration and performance enhancement. Stay tuned!
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