Coluracetam is a recently developed Nootropic agent that falls in the popular class of Racetams. This Nootropic agent is believed to be an effective cognitive enhancer. The structural composition of Coluracetam includes a Racetam compound that is synthesized from Piracetam (Note that Piracetam was the first Nootropic to be developed in the early 1960s). Also, it is ethanol soluble. Coluracetam was initially registered, developed, and tested in Japan by Mitsubishi Tanabe Pharma Corporation mainly for Alzheimer’s disease back in 2005, but its clinical trials using larger samples of patients failed to give substantial results in Phase II. With only a third of the study subjects showing positive effects and no evidence of delay in the progress of the disease, it has been marketed as a cognitive enhancer ever since. The patent for Coluracetam was later reallocated to another corporation known as BrainCells Inc., which is currently in charge of carrying out research on the substance. BrainCells Inc. has been focusing much of its tests on this product for its effects on general anxiety and major depression disorder (MDD).
Coluracetam is unique compared to other Nootropics because it is the sole high-affinity choline uptake (HACU) enhancer even in dead or damaged neurons. This substance has taken the center stage because of its exceptional effects on the cholinergic system. Although not much evidence has been obtained from studies, the mechanism by which Coluracetam acts seems to vary substantially from other close nootropics especially racetams like Aniracetam and Piracetam. Coluracetam is also referred to as MKC-231 or BCI-540. Its structural name is 2-(2-oxopyrrolidin-1-yl)-N-(2, 3-dimethyl-5, 6, 7, 8-tetrahydrofuro2, 3-b quinolin-4-yl)acetamide. Although scientists had information on the molecular composition of Coluracetam for many years, its commercial production only began recently due to challenges in its synthesis. The substance was made available for use to the general public in 2013, and it became popular to nootropic agent users rapidly because of its cognitive effects. This nootropic is currently not used in large scale.
One of the latest milestones achieved in the commercial production of Coluracetam can be traced back to September 2012 when a Longecity forum user known as “ScienceGuy” made his contribution to help produce Coluracetam for nootropic agent’s fans. He used his personal finances approximately 16,000 U.S. dollars to contract a Europe based laboratory to manufacture 500 gm of this nootropic from scratch. HNMR and HPLC analysis was conducted on the final product to verify that the sample was of the highest purity. Following six months of experimentation and production, ScienceGuy provided his planning and anecdotal observation after having done thorough personal documentation. He gave an expansive explanation detailing his entire procedure and then issued 40 samples of the final product to participants in the forum. The participants were given an opportunity to test the nootropic agent and give testimony on their experiences.
BrainCells Inc., the company, holding the patent to Coluracetam targets to develop the substance as a prophylactic therapy against or actual treatment of peripheral and central nervous system diseases. These diseases include mood, memory, learning, degenerative, ischemic, anxiety, psychosis, and trauma disorders. The foundations of this patent are the impacts of Coluracetam on brain cell differentiation and neural stem cell culture analysis. Most of the research conducted hints that Coluracetam may particularly be effective in brain parts related to visual processing, and, therefore, it has a high potential for future use in clinical treatment for retina and optic nerve damages.
A study conducted in 1994 using lab rats as study subjects revealed that Coluracetam was able to reverse the deficiencies in working memory and fall in acetylcholine levels in the hippocampus. The effects of the substance were observed when it was administered in chronic levels. Compared to other Nootropics (Tetrahydroaminoacridine and Linopirdine), these effects were considerably higher. Significant effects were noted to be considerable when Coluracetam was administered orally in an eleven-day trial whereby administration consisted of three dosages of once per day in the range of 0.3, 1.0, and 3.0 mg/kg.
In 1996, a study that involved comparative tests between Coluracetam and Tacrine (an acetylcholinesterase) using a mice model proved that Coluracetam had an advanced effect on the HACU system but particularly in diseased rats and no effects were observed in normal rats. The observed effects of Coluracetam in the diseased rodents included; improved memorization and water maze learning and no key signs of any side effects were noted. On the other hand, Tacrine even when administered in high dosages did not exhibit any effects on learning process but had side effects that included tremor, salivation or hypothermia. Another rat modeled study that involved using phencyclidine, cocaine, and carbachol to induce schizophrenia in 2007 attempted to find out if Coluracetam could be effective in the treatment of behavioral and cellular deficits that are linked to exposure. Coluracetam was found to reverse the locomotor dysfunction observed in mice that had been exposed to cocaine and carbachol. It was also seen to reverse the cognitive deficits observed after the mice were exposed to phencyclidine. The Nootropic agent was also observed to stop the decrease in choline acetyltransferase cells found in the medial septum that are necessary for the synthesis of acetylcholine. However, even if the results were positive, they showed that more tests were necessary to ascertain the chances of Coluracetam to function as a cure for schizophrenia. NOTE: Phencyclidine is a research drug used in scientific studies to induce the symptoms related to schizophrenia.
Another study was carried out in 2008, in which the researchers were following up on their tests on water-maze learning using mice that had cognitive impairments. The mice were administered with 1-3 mg/kg of Coluracetam and observations were made to determine the effects of the substance on learning and HACU system within intervals of 1 hour and 24 hours of administration. Also, observations were made after 48 hours and 72 hours following administration. The results showed cognitive enhancement at 24 hours. The rodents showed improvements in remembering the right path when navigating the Morris Water Maze. The behavior of HACU in due course demonstrated increase suggesting that there was a longer-term and sustained reverse of cognitive deficits despite administration of the last dose. The fact that these memory improvements were persistent after Coluracetam had left the system of the rodents implies that this nootropic has some long-term structural alterations. In this same study, when rats that had been treated with choline uptake inhibitors like AF64A were administered with Coluracetam, they showed signs of increased choline uptake and a higher rate of acetylcholine synthesis. In rats that had not been treated with choline uptake inhibitors, HACU did not exhibit any signs of effects in hippocampal slices. Also, ligand (HC-3) connected to cholinergic receptors in the case of normal rats appeared to be intact. As such, Coluracetam may be able to enhance learning effects observed in choline uptake inhibitors as revealed in water maze tests after oral administration at doses in the range of 1-10mg/kg in lab rats. A single administration of 300-3,000mcg of Coluracetam did not show any effects but when administered for 12 days, the effects were positive with the performance of the rats in a T-maze being almost perfect. In this AF64A treated research model, positive effects in cognition were observed at 1-3mg/kg of Coluracetam. These effects were still visible even two days after administration of Coluracetam was terminated, and no traces of the substance were detectable in the brain. On the third day, the benefits were not significant.
Human trials performed by BrainCells Inc. that aimed at testing the ability of Coluracetam to function as a neurogenesis enhancer in the treatment of anxiety and depression provided positive results. Currently, Phase 2A of the human clinical trial has been finalized, and the results show that Coluracetam has a high potential in treating the two conditions. A large number of patients who had reported little or no benefits after using other anti-depressants found Coluracetam to be effective for them. About 365 of the patients involved in the study showed major improvements when evaluated on the severity of anxiety and depression. The experimental group of patients was administered with 80gm of Coluracetam that was taken either once or three times per day for six weeks. The sub-group administered with a dose 3-times a day had treatment success of 36% while the placebo sub-group reported 19% success. The group administered with a single dose per day did not provide statistically reliable results.
A considerable number of the participants also reported that they had experienced other additional benefits from Coluracetam supplements consumption that included reduced stress and a feeling of well-being and contentment. Some patients reported Coluracetam to be very effective when stacked since it can increase the efficacy of other nootropic agents and still provide improvements to vision. These clinical trials were encouraged by the role of the hippocampus on mood disorders, the impact of neurogenesis on the hippocampus, and the role coluracetam plays in this process. An earlier research carried out in Japan by Mitsubishi Tanabe Pharma Corporation had failed to provide results on Coluracetam’s clinical efficacy, although it proved the beliefs on its mechanism of action, which entails the uptake of choline in the brain.
There is limited statistical evidence to support the use of Coluracetam to enhance cognition process. More clinical studies are necessary to determine if Coluracetam has a therapeutic role in cases whereby HACU may be damaged, as in Alzheimer’s disease.