coluracetam
Coluracetam reached a 115-person depression-and-anxiety trial, but the sponsor reported no overall benefit. A single healthy-user case found no significant objective cognitive change, and the positive memory work remains confined to chemically impaired animals.
Small-molecule investigational racetam
- The phase 2 registry enrolled 115; its sponsor reported no overall depression or anxiety advantage among 101 evaluable participants.
- A favorable 80 mg three-times-daily/GAD subgroup lacks its denominator, confidence interval and prespecified analysis status.
- The only published healthy-user report is an uncontrolled n=1 with a null pooled objective pre/post comparison.
- No quantitative human pharmacokinetic study is reported in the cited records.
What are MKC-231 and BCI-540?
MKC-231 and BCI-540 are development names for coluracetam, an investigational racetam studied in cholinergic injury models and one human mood-disorder trial.
The phase 2 study used 80 mg once daily or 80 mg three times daily. The one-person report used an unassayed capsule labeled 20 mg/day. Neither establishes a consumer regimen or verifies retail material.
PubChem: coluracetam chemical identity
Government chemical identity database
National Library of Medicine. PubChem CID 214346.
C19H23N3O3; molecular weight 341.4 g/mol.
- Participants / model
- Chemical record
- Follow-up
- Living database
- Study design
- Curated structure record
Formula and molecular weight establish the recorded structure, not the contents of a retail product or an effective dose.
Read the original sourceMKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice.
Preclinical mouse study
Murai S, Saito H, Abe E, Masuda Y, Odashima J, Itoh T. Journal of Neural Transmission. 1994. PMID 7710736. DOI 10.1007/BF01277590.
Repeated administration improved a working-memory deficit and hippocampal acetylcholine depletion in an induced-injury model; the acute behavioral experiment was negative.
- Participants / model
- AF64A-treated mice
- Follow-up
- Repeated treatment for 11 days
- Study design
- Behavioral and neurochemical experiments
An induced cholinergic lesion and maze performance do not establish healthy human benefit.
Read the original sourceSafety and Effectiveness Study of BCI-540 Versus Placebo in the Treatment of Major Depressive Disorder With Concomitant Anxiety
Clinical trial registry
BrainCells Inc. NCT00621270, BCI-540-CL-001.
The phase 2 trial enrolled 115 participants with major depressive disorder and concomitant anxiety.
- Participants / model
- Adults with major depression and concomitant anxiety
- Follow-up
- Completed October 2009
- Study design
- Interventional randomized placebo comparison
The registry confirms that the study was registered; it does not report outcomes establishing success.
Read the original sourceWhat happened in the memory experiments?
Repeated MKC-231 improved maze performance and partly restored cholinergic measures after researchers chemically damaged the animals’ cholinergic systems.
A single acute treatment was behaviorally null in the mouse study. In rats, choline uptake increased in lesioned but not normal synaptosomes. These results support condition-dependent pharmacology, not memory enhancement in an intact human brain.
MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice.
Preclinical mouse study
Murai S, Saito H, Abe E, Masuda Y, Odashima J, Itoh T. Journal of Neural Transmission. 1994. PMID 7710736. DOI 10.1007/BF01277590.
Repeated administration improved a working-memory deficit and hippocampal acetylcholine depletion in an induced-injury model; the acute behavioral experiment was negative.
- Participants / model
- AF64A-treated mice
- Follow-up
- Repeated treatment for 11 days
- Study design
- Behavioral and neurochemical experiments
An induced cholinergic lesion and maze performance do not establish healthy human benefit.
Read the original sourceEffect of the novel high affinity choline uptake enhancer 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b] quinolin-4-yl)acetoamide on deficits of water maze learning in rats.
Preclinical primary study
Bessho T, Takashina K, Tabata R, Ohshima C, Chaki H, Yamabe H, Egawa M, Tobe A, Saito K. Arzneimittelforschung. 1996. PMID 8740080.
MKC-231 increased high-affinity choline uptake in AF64A-treated but not normal rat synaptosomes and improved water-maze deficits in lesioned rats.
- Participants / model
- AF64A-treated rats and ex-vivo synaptosomes
- Follow-up
- Repeated animal treatment
- Study design
- Controlled lesion-model experiments
This is induced cholinergic-damage rescue, not healthy-human cognition or proof that added choline helps.
Read the original sourceDid the human depression-and-anxiety trial work?
Among 101 evaluable participants, the sponsor reported no overall depression or anxiety advantage over placebo. The registry enrolled 115 adults.
A later “further analysis” reported 36% response with 80 mg three times daily versus 19% with placebo and a 12.2-versus-5.5-point HAM-D change in a comorbid-GAD subgroup. The subgroup denominator, confidence interval, multiplicity control and prespecified status were not disclosed.
The registry names IDS-C30 and HAM-A as co-primary outcomes, while the sponsor release discusses HAM-D and HAM-A. That mismatch prevents treating the subgroup p<0.008 as a confirmed registered-primary result.
Safety and Effectiveness Study of BCI-540 Versus Placebo in the Treatment of Major Depressive Disorder With Concomitant Anxiety
Clinical trial registry
BrainCells Inc. NCT00621270, BCI-540-CL-001.
The phase 2 trial enrolled 115 participants with major depressive disorder and concomitant anxiety.
- Participants / model
- Adults with major depression and concomitant anxiety
- Follow-up
- Completed October 2009
- Study design
- Interventional randomized placebo comparison
The registry confirms that the study was registered; it does not report outcomes establishing success.
Read the original sourceBrainCells announces top-line BCI-540 phase 2 results in depression and anxiety.
Primary sponsor results disclosure
BrainCells Inc. Archived sponsor results release. 2010.
BCI-540 did not outperform placebo on overall depression or anxiety outcomes; a further-analysis 80 mg three-times-daily subgroup with comorbid GAD was favorable.
- Participants / model
- 101 evaluable adults from the 115-person phase 2 trial
- Follow-up
- Six weeks
- Study design
- Sponsor top-line disclosure for a randomized double-blind placebo-controlled trial
Subgroup size, confidence intervals, multiplicity control and prespecification are absent; the registry and release name different depression scales.
Read the original sourceDoes the published healthy-user case prove better cognition or vision?
One unblinded man used coluracetam for three months while also changing exercise, diet, and sleep. His pooled objective pre/post cognitive comparison found no improvement.
He reported brief headaches, later sharper vision and easier writing, but no standardized eye examination or color-vision endpoint was used. Correlation across five subscale scores does not test a drug effect, and he chose not to continue.
The Effects of Cognitive Enhancement Drug (Coluracetam) on Visual Perception, Abstract Reasoning, Pattern Recognition, Spatial Orientation, and Analytical Thinking: A Case Study
Primary human case report
Villarino ML, Villarino RT. The Effects of Cognitive Enhancement Drug (Coluracetam) on Visual Perception, Abstract Reasoning, Pattern Recognition, Spatial Orientation, and Analytical Thinking: A Case Study. International Journal of Cognition & Behaviour. 2023. DOI 10.23937/2690-3172/1710016.
One healthy user had no significant pooled objective pre/post cognitive difference (t=-0.33, p=0.75) despite subjective vision and writing reports.
- Participants / model
- One healthy 36-year-old man
- Follow-up
- 20 mg/day for three months
- Study design
- Unblinded uncontrolled before/after case report
Exercise, diet, sleep, practice, expectation and an unassayed capsule confound attribution; the reported correlation is not a treatment comparison.
Read the original sourceWhy was coluracetam studied for gut pain?
Chinese researchers used MKC-231 as a choline-transporter probe in stressed rats and reported less visceral-pain behavior.
Sixty male rats entered four groups, with key pain comparisons reported in six per group. Treatment began before stress, no human IBS patient was treated, and transporter blockade did not prove the proposed mechanism caused the behavior.
Upregulation of the high-affinity choline transporter in colon relieves stress-induced hyperalgesia
Preclinical primary rat study
Lin MJ, Yu BP. Journal of Pain Research. 2018. DOI 10.2147/JPR.S164186.
MKC-231 altered colonic choline-transporter expression and reduced stress-associated visceral pain measures.
- Participants / model
- 60 male rats assigned to four groups; key pain assays reported n=6 per group
- Study design
- Controlled animal mechanistic experiments
- Funding
- National Natural Science Foundation of China grants 81170351 and 81770638.
Treatment preceded repeated stress. No baseline behavior was measured, choline transport function was not directly tested and no transporter-blockade experiment established causal mediation. This is not a human IBS trial.
Read the original sourceWhat is actually known about safety and exposure?
The sponsor said trial tolerability resembled placebo but published no arm-level counts, event list, discontinuations, laboratory table, or long-term follow-up.
The one-person report described transient headache. The cited records contain no primary quantitative human PK report, so repeated web claims of a 30-minute peak or short half-life lack support from quantitative human data.
FDA names coluracetam in an unapproved-drug distribution case. That establishes US regulatory history, not a toxicity rate or the identity of any current product.
BrainCells announces top-line BCI-540 phase 2 results in depression and anxiety.
Primary sponsor results disclosure
BrainCells Inc. Archived sponsor results release. 2010.
BCI-540 did not outperform placebo on overall depression or anxiety outcomes; a further-analysis 80 mg three-times-daily subgroup with comorbid GAD was favorable.
- Participants / model
- 101 evaluable adults from the 115-person phase 2 trial
- Follow-up
- Six weeks
- Study design
- Sponsor top-line disclosure for a randomized double-blind placebo-controlled trial
Subgroup size, confidence intervals, multiplicity control and prespecification are absent; the registry and release name different depression scales.
Read the original sourceThe Effects of Cognitive Enhancement Drug (Coluracetam) on Visual Perception, Abstract Reasoning, Pattern Recognition, Spatial Orientation, and Analytical Thinking: A Case Study
Primary human case report
Villarino ML, Villarino RT. The Effects of Cognitive Enhancement Drug (Coluracetam) on Visual Perception, Abstract Reasoning, Pattern Recognition, Spatial Orientation, and Analytical Thinking: A Case Study. International Journal of Cognition & Behaviour. 2023. DOI 10.23937/2690-3172/1710016.
One healthy user had no significant pooled objective pre/post cognitive difference (t=-0.33, p=0.75) despite subjective vision and writing reports.
- Participants / model
- One healthy 36-year-old man
- Follow-up
- 20 mg/day for three months
- Study design
- Unblinded uncontrolled before/after case report
Exercise, diet, sleep, practice, expectation and an unassayed capsule confound attribution; the reported correlation is not a treatment comparison.
Read the original sourceFDA: unapproved racetam distribution case
Official enforcement record
US FDA / US Department of Justice. Arizona company and CEO plead guilty to distribution of drugs not approved by FDA. 2023.
The case identifies piracetam, aniracetam, coluracetam, and phenylpiracetam among unapproved drugs marketed online.
- Participants / model
- United States distribution
- Follow-up
- 2023
- Study design
- Official case record
This establishes the named US enforcement history, not every country’s status or a quantified rate of injury.
Read the original sourceStudies and sources
MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice.
Preclinical mouse study
Murai S, Saito H, Abe E, Masuda Y, Odashima J, Itoh T. Journal of Neural Transmission. 1994. PMID 7710736. DOI 10.1007/BF01277590.
Repeated administration improved a working-memory deficit and hippocampal acetylcholine depletion in an induced-injury model; the acute behavioral experiment was negative.
- Participants / model
- AF64A-treated mice
- Follow-up
- Repeated treatment for 11 days
- Study design
- Behavioral and neurochemical experiments
An induced cholinergic lesion and maze performance do not establish healthy human benefit.
Read the original sourceSafety and Effectiveness Study of BCI-540 Versus Placebo in the Treatment of Major Depressive Disorder With Concomitant Anxiety
Clinical trial registry
BrainCells Inc. NCT00621270, BCI-540-CL-001.
The phase 2 trial enrolled 115 participants with major depressive disorder and concomitant anxiety.
- Participants / model
- Adults with major depression and concomitant anxiety
- Follow-up
- Completed October 2009
- Study design
- Interventional randomized placebo comparison
The registry confirms that the study was registered; it does not report outcomes establishing success.
Read the original sourceFDA: unapproved racetam distribution case
Official enforcement record
US FDA / US Department of Justice. Arizona company and CEO plead guilty to distribution of drugs not approved by FDA. 2023.
The case identifies piracetam, aniracetam, coluracetam, and phenylpiracetam among unapproved drugs marketed online.
- Participants / model
- United States distribution
- Follow-up
- 2023
- Study design
- Official case record
This establishes the named US enforcement history, not every country’s status or a quantified rate of injury.
Read the original sourcePubChem: coluracetam chemical identity
Government chemical identity database
National Library of Medicine. PubChem CID 214346.
C19H23N3O3; molecular weight 341.4 g/mol.
- Participants / model
- Chemical record
- Follow-up
- Living database
- Study design
- Curated structure record
Formula and molecular weight establish the recorded structure, not the contents of a retail product or an effective dose.
Read the original sourceUpregulation of the high-affinity choline transporter in colon relieves stress-induced hyperalgesia
Preclinical primary rat study
Lin MJ, Yu BP. Journal of Pain Research. 2018. DOI 10.2147/JPR.S164186.
MKC-231 altered colonic choline-transporter expression and reduced stress-associated visceral pain measures.
- Participants / model
- 60 male rats assigned to four groups; key pain assays reported n=6 per group
- Study design
- Controlled animal mechanistic experiments
- Funding
- National Natural Science Foundation of China grants 81170351 and 81770638.
Treatment preceded repeated stress. No baseline behavior was measured, choline transport function was not directly tested and no transporter-blockade experiment established causal mediation. This is not a human IBS trial.
Read the original sourceBrainCells announces top-line BCI-540 phase 2 results in depression and anxiety.
Primary sponsor results disclosure
BrainCells Inc. Archived sponsor results release. 2010.
BCI-540 did not outperform placebo on overall depression or anxiety outcomes; a further-analysis 80 mg three-times-daily subgroup with comorbid GAD was favorable.
- Participants / model
- 101 evaluable adults from the 115-person phase 2 trial
- Follow-up
- Six weeks
- Study design
- Sponsor top-line disclosure for a randomized double-blind placebo-controlled trial
Subgroup size, confidence intervals, multiplicity control and prespecification are absent; the registry and release name different depression scales.
Read the original sourceThe Effects of Cognitive Enhancement Drug (Coluracetam) on Visual Perception, Abstract Reasoning, Pattern Recognition, Spatial Orientation, and Analytical Thinking: A Case Study
Primary human case report
Villarino ML, Villarino RT. The Effects of Cognitive Enhancement Drug (Coluracetam) on Visual Perception, Abstract Reasoning, Pattern Recognition, Spatial Orientation, and Analytical Thinking: A Case Study. International Journal of Cognition & Behaviour. 2023. DOI 10.23937/2690-3172/1710016.
One healthy user had no significant pooled objective pre/post cognitive difference (t=-0.33, p=0.75) despite subjective vision and writing reports.
- Participants / model
- One healthy 36-year-old man
- Follow-up
- 20 mg/day for three months
- Study design
- Unblinded uncontrolled before/after case report
Exercise, diet, sleep, practice, expectation and an unassayed capsule confound attribution; the reported correlation is not a treatment comparison.
Read the original sourceEffect of the novel high affinity choline uptake enhancer 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b] quinolin-4-yl)acetoamide on deficits of water maze learning in rats.
Preclinical primary study
Bessho T, Takashina K, Tabata R, Ohshima C, Chaki H, Yamabe H, Egawa M, Tobe A, Saito K. Arzneimittelforschung. 1996. PMID 8740080.
MKC-231 increased high-affinity choline uptake in AF64A-treated but not normal rat synaptosomes and improved water-maze deficits in lesioned rats.
- Participants / model
- AF64A-treated rats and ex-vivo synaptosomes
- Follow-up
- Repeated animal treatment
- Study design
- Controlled lesion-model experiments
This is induced cholinergic-damage rescue, not healthy-human cognition or proof that added choline helps.
Read the original sourceWhy is coluracetam in D tier?
D reflects an overall-null randomized mood trial, an incompletely reported subgroup signal, one uncontrolled healthy case with null objective testing, and lesion-model animal plausibility. Healthy cognition, vision and routine safety remain unestablished.