Coluracetam is a drug purported to have cognitive- and memory-enhancing benefits.
Research is ongoing to determine its efficacy and safety, yet researchers are hopeful with the limited results of early in vivo and in vitro studies.
Coluracetam belongs to a class of synthetic racetam drugs â€” drugs that share a structure called a pyrrolidone nucleus and are classified as a nootropic, or â€śsmart drug.â€ť Nootropics are thought to enhance cognition and memory (1). Coluracetam is sometimes referred to as MKC-231 and BCI -540.
Coluracetam appears to interact with a process known as high affinity choline uptake (HACU) â€” the system in which choline is converted into acetylcholine. Â Acetylcholine is an important neurotransmitter for memory, mood, muscle control and other brain and nervous system functions (2).
This neurotransmitter is depleted in the brain by Alzheimerâ€™s disease and other neurodegenerative diseases (3). Researchers are hopeful that coluracetam may play a therapeutic role in the treatment for such diseases.
Coluracetam is shown to provide cognitive improvement in animal studies. The aim of a 2008 study was to examine the effect of MKC-231 on acetylcholine synthesis and release in the hippocampus of rats with impaired working memory.
Rats were administered ethylcholine aziridinium ion (used to develop an animal model of Alzheimerâ€™s disease or senile dementia of Alzheimer’s type).
Single oral administration of MKC-231 showed a significant reversal in the decrease of both HACU and acetylcholine release in the impaired rats. These results indicate MKC-231 improves cholinergic hypofunction by enhancing HACU, subsequently facilitating acetylcholine synthesis and release.
Hoping to build on the results of the previous study, researchers performed another study, this time investigating the effects of repeated administration of MKC-231, rather than a single dose. Rats were treated with 1 and 3 mg/kg, p.o. for eight days and were evaluated for learning impairment. Significant cognitive improvement was observed.
They also studied the effects of eight-days of repeated administration of MKC-231 on high affinity choline uptake and concluded that MKC-231 could induce long-lasting pro-cognitive effects by changing the choline transporter regulation system (4).
Further studies are needed, especially in humans to see if it has a therapeutic role in instances where HACU may be impaired â€” such as Alzheimer’s disease.
Coluracetam may have neuroprotective properties. Japanese researchers performed a study to examine the neuroprotective action of MKC-231 in rats. Glutamate neurotoxicity (characterized by an increasing damage of cell components, including mitochondria, leading to cell death) was assessed with cortical cultures obtained from fetal rats.
An improvement in glutamate neurotoxicity is promising due to the fact that neurotoxicity is strongly associated with acute brain injury, such as that produced by a stroke, as well as certain chronic neurodegenerative diseases including Alzheimerâ€™s and Huntingtonâ€™s disease and other diseases of the nervous system (7).
One study shows coluracetam may be a potential therapeutic drug for the treatment of schizophrenia. In a 2007 study, published in European Neuropsychopharmacology, an animal model of rats administered phencyclidine (a research drug to induce symptoms associated with schizophrenia), carbachol and cocaine sought to determine if treatment with coluracetam alleviated the cellular and behavioral deficits associated with exposure to phencyclidine.
The results showed that coluracetam reversed the locomotor dysfunction noted in rats exposed to carbachol and cocaine as well as the cognitive deficits noted following phencyclidine exposure (8).
In addition, the drug also halted the decline in choline acetyltransferase cells; choline acetyltransferase is needed for cholinergic neurons to communicate with target cells and a decline of it is associated with disorders such as Alzheimer’s disease and schizophrenia (9).
The results suggest further studies are warranted to better understand coluacetamâ€™s role in the possible treatment of schizophrenia.
One study shows the ability of coluracetam to treat depression. Major depressive disorder (or clinical depression) is a serious medical illness that affects the way someone feels, acts and thinks. According to the American Psychiatry Association, one in six people will experience depression in their lifetime (10).
The purpose of a 2010 study was to evaluate the ability of BCI -540 to treat major depressive disorder in patients also suffering from general anxiety disorder who fail to respond to two other types of antidepressants. Â The six-week trial was randomized, double-blind and placebo-controlled to determine whether 80 milligrams of BCI -540 taken orally once or three times daily alleviated symptoms.
Researchers measured change with a variety of commonly used patient and physician-rated scales including the Hamilton Rating Scales for Anxiety (HAM-A) and Depression (HAM-D).
Researchers determined that in patients who received BCI -540 three times a day, 36 percent showed an improvement compared to 19 percent in the placebo group. BCI -540 was also found to be well tolerated during the six-week trial (11).
It is important to note that this is the only study thus far performed on humans. In-depth human studies are needed to better understand its mechanism, efficacy and long-term effects.
There are no known side effects due to insufficient clinical studies performed on humans.
Due to a lack of human clinical studies, there is no recommended dosage for coluracetam at this time.
Coluracetam is synthetic racetam drug believed to have cognitive-enhancing benefits. Research is ongoing to determine its efficacy and safety, yet researchers are hopeful with the results of early in vivo and in vitro studies.
The exact mechanism of action of coluracetam (also referred to as MKC-231 and BCI -540 in clinical studies) has not yet been clearly established, but researchers believe coluracetam boosts the brainâ€™s choline conversion to acetylcholine through the high affinity choline uptake (HACU) process.
Acetylcholine is an important neurotransmitter for memory, mood, muscle control and other brain and nervous system functions.
Limited studies also show coluracetamâ€™s neuroprotective property and potential to be a treatment for schizophrenia and major depressive disorder.
Since cholinergicÂ deficits areÂ reportedÂ toÂ causeÂ cognitiveÂ impairmentsÂ in Alzheimerâ€™s diseaseÂ as well as mild cognitive impairment and other psychiatricÂ diseasesÂ Coluracetam might provide hope as a new therapeutic treatment for such diseases.
It is important to note that studies have been limited to in vitro and in vivo studies using animals and not humans. Â Whatâ€™s more, many of these studies were performed in the 90s and early 2000s, highlighting the need for modern studies.