A GABA derivative with multiple actions

Piracetam is a member of a group of nootropic racetams called the “primary racetams” which includes: piracetam, aniracetam and oxiracetam. Dr. Corneliu Giurgea began developing the racetams in the 1970‘s in Belgium, but his first entry into the field of nootropic research was piracetam. Incidentally, Dr. Giurgea not only coined the term nootropic (derived from the Greek “noos” meaning mind and the Greek “tropein” meaning to turn) but also derived the initial criterion by which a true nootropic substance must be measured.

Piracetam was produced as a cyclic derivative of GABA (Gamma-Amino-Butyric acid) however, it’s effects are nothing similar to GABA. This nootropic was created from the 2-pyrolidinone structure which was then aminated. 2-pyrolidinone is a common structure when dealing with the racetams. It is the basic backbone of all the classic racetams and the absence of this common core structure is what separates noopept (apart from it being a peptide) from being a true “racetam.”

As far as how piracetam actually does work, that’s still evidently a matter of debate, but owing to the success of the substance when tested through multiple means this could just suggest that it’s a combination of factors or some synergy between multiple mechanisms of action that piracetam owes it’s function to. As far as some of the ways piracetam reacts with the body, firstly it provides excellent blood-brain-barrier penetration. In addition, it has an influence upon neuronal and vascular functioning which in turn improves cerebral brain flow. Increased glucose efficiency within the brain may be another mechanism that aids in piracetam nootropic functions.

All these functions taken together optimize cell maintenance and upkeep tasks which can improve overall brain functioning. In addition this improvement of nutrition and excretion tasks may help prevent the build-up of the neurotoxin lipofuscin which can speed up age related mental decline. In addition the increased neuronal fluidity may lead to improved neuronal communication, increasing the signal transmission of brain cells. Lipofuscin build up also occurs in the brain damage resultant in severe alcoholism and studies have actually been performed that may suggest that piracetam may be helpful in restoring damaged functions due to stroke, trauma, age or even drug and alcohol abuse.

Piracetam’s Effects on AMPA and Glutamatergic System

Piracetam evidently has some glutamatergic effects as well. Glutamate, in addition to being one of the most abundant enzymes in the body is also one of the body’s primary excitatory neurotransmitters. It’s this excitatory activity that could be linked to piracetam’s ability to act as a psychostimulant without offering any peripheral nervous system or CNS stimulation whatsoever.

Piracetam is actually also a weak AMPAkine. It acts as a positive modulator of AMPA (one of the subsets of glutamate receptor types which is directly linked to neural plasticity and long-term potentiation, the process by which memories are permanently stored to be retrieved any time). Lipofuscin build-up is one of the possible negative side effects of severe alcoholism that leads to the possibility of resultant brain damage. Piracetam has been studied in cases of severe alcoholism to be helpful in reversing some of the negative damage done by drug abuse as well as organic brain damage, age related cognitive decline and ischemic stroke.

One of piracetams’s most well known mechanisms of action is as a cholinergic substance. Cholinergic means acting upon the acetylcholine system. Acetylcholine, the brain’s key learning, memory and movement neurotransmitters is vital to memory formation, storage and recall especially short-term or “working memory” which is vital to fluid intelligence. Your working memory would be like the RAM in your computer. It doesn’t matter how much data you have stored in your cerebral hard drive if you don’t have enough RAM to access and manipulate it with any fluency.

Piracetam’s Potent Neuroprotective Powers

Piracetam in addition to being a possible cognitive enhancer is a very potent neuroprotective substance. Reduction of oxidative stress due to drug and alcohol use (as mentioned before) is one of the neuroprotective functions. It’s cholinergic effect seems to be a possible boon to those suffering from Alzheimer’s and dementia as well. Piracetam’s labeled use is as a neuroprotective agent and has shown usefulness in improving cerebral function to those who have recently suffered stroke or to reduce the risk of ischemic stroke. As an anti-coagulant and anti-thrombotic agent it’s even been shown as helpful as aspirin as a daily blood thinning agent.

Piracetam also interacts with Calcium channels and calcium ions (Ca+). In cases of excessive neuronal firing it can calm the over-stimulated brain. This calcium influx is also part of what leads to piracetam’s ability to increase membrane fluidity. Membrane fluidity is lost in cases of oxidative and lipid peroxidative stress. Oxidation is the situation where oxygen (which despite being a necessity for human life, is highly caustic) breaks down matter. A good example of this is FeO2 (Ferric Oxide, more commonly known as rust). This “rusting” behavior happens to cells in your body and this is what the “oxidative” process is referring to. Piracetam can increase cerebral plasticity while maintaining membrane fluidity.

In certain cases where excessive cases of oxidative stress were noted, the fluidity of mitochondria were also affected. Since mitochondrial energy is the energy currency of the body and decreases after the age 30 and decrease in mitochondrial fluidity is correlated to age related cognitive issues.

Some researchers argue piracetam is less of a cognitive enhancer in a fully optimized mind but can bridge the gap between certain deficits and certainly provides for healthier overall cognitive function and is nearly as neuro-protective as it is neurotoxic seeing as it’s LD-50 (the amount on average that constitutes a “lethal dosage”) is higher than that of salt or water by volume it’s technically safe as salt, just remember to take that with a grain and not a whole bottle!