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Coluracetam

Coluracetam is a lab-developed compound that boosts how nerve cells take up choline, the raw material for acetylcholine, a chemical messenger involved in learning and memory. In rodents with impaired cholinergic function, it preserved and increased choline uptake and improved maze learning and working memory. The evidence is very limited, though: it is mostly animal work, and company trials in Alzheimer's disease and depression with anxiety did not show benefit.

Sources: PMID 8825012; PMID 8799197; PMID 9225290

Best evidence
Grade D
Conditions studied
3
Outcomes
6
Graded outcomes
0006

Evidence by condition

  • Strong
  • Moderate
  • Limited
  • Very limited

3 conditions, plus general outcomes

General

General: outcomes studied for Coluracetam
GradeOutcomeEffectSizeStudiesPeopleStudies list
High-Affinity Choline Uptake (HACU)

In rodent models with pharmacologically impaired cholinergic function (AF64A and ethylcholine aziridinium), coluracetam (MKC-231) consistently preserved and enhanced high-affinity choline uptake, increasing Vmax of HACU and Bmax of HC-3 binding approximately 1.6-1.7 fold. Effects appear specific to impaired HACU rather than enhancing normal function.

Improves (the measure goes up)Moderate effect8 studies

Studies that measured high-affinity choline uptake (hacu)

Acetylcholine Synthesis and Release

In AF64A-treated rats with reduced hippocampal acetylcholine, coluracetam significantly reversed decreases in ACh synthesis and release. The effect is mediated through enhanced choline transport rather than acetylcholinesterase inhibition, distinguishing it mechanistically from donepezil-class drugs.

Improves (the measure goes up)Moderate effect2 studies

Studies that measured acetylcholine synthesis and release

Cholinergic Neuroprotection (PCP Model)

In a single rat study, subsequent exposure to coluracetam antagonized phencyclidine (PCP)-induced behavioral deficits and reduction in septal cholinergic neurons, suggesting potential neuroprotective properties for cholinergic pathways under neurotoxic stress.

Improves (the measure goes up)Small effect2 studies

Studies that measured cholinergic neuroprotection (pcp model)

Age-Associated Memory Impairment and Cognitive Decline (AAMCD)

Age-Associated Memory Impairment and Cognitive Decline (AAMCD): outcomes studied for Coluracetam
GradeOutcomeEffectSizeStudiesPeopleStudies list
Learning and Memory (Cholinergic Deficit Models)

In AF64A-treated rats and mice with cholinergic deficits, oral coluracetam (1-10 mg/kg) significantly improved water maze learning and working memory deficits. Repeated administration produced long-lasting cognitive improvement persisting 24-72 hours after the last dose, suggesting durable changes to choline transporter regulation. No cognitive enhancement was observed in normal (non-impaired) animals.

Improves (the measure goes up)Moderate effect7 studies

Studies that measured learning and memory (cholinergic deficit models)

Alzheimer’s Disease

  • Alzheimer's Disease Symptoms: improves
Alzheimer’s Disease: outcomes studied for Coluracetam
GradeOutcomeEffectSizeStudiesPeopleStudies list
Alzheimer's Disease Symptoms

Mitsubishi Tanabe Pharma conducted a Phase 2a clinical trial for Alzheimer's disease. The trial failed to meet efficacy endpoints and development was discontinued for this indication. Despite a plausible HACU-based mechanism, human evidence does not support benefit in Alzheimer's disease.

Improves (the measure goes down)Small effect

Anxiety Disorders (Other)

  • Depression and Anxiety Symptoms: improves
Anxiety Disorders (Other): outcomes studied for Coluracetam
GradeOutcomeEffectSizeStudiesPeopleStudies list
Depression and Anxiety Symptoms

BrainCells Inc. conducted a Phase 2 clinical trial for major depressive disorder with comorbid generalized anxiety disorder. Primary endpoints were not met — no significant benefit over placebo was demonstrated. Development for this indication was discontinued.

Improves (the measure goes down)Small effect

Key findings

  • High-Affinity Choline Uptake (HACU)Improves (the measure goes up)
  • Learning and Memory (Cholinergic Deficit Models)Age-Associated Memory Impairment and Cognitive Decline (AAMCD)Improves (the measure goes up)
  • Acetylcholine Synthesis and ReleaseImproves (the measure goes up)

Shop Coluracetam

Third-party tested Coluracetam products. The evidence above is limited, so read it before you buy.

  • Grade D

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Studies cited

10 studies from PubMed

  1. MKC-231, a choline-uptake enhancer: (1) long-lasting cognitive improvement after repeated administration in AF64A-treated ratsJournal of Neural Transmission, 2008 · PMID 18461272
  2. MKC-231, a choline uptake enhancer: (2) Effect on synthesis and release of acetylcholine in AF64A-treated ratsJournal of Neural Transmission, 2008 · PMID 18446264
  3. MKC-231, a choline uptake enhancer: (3) Mode of action of MKC-231 in the enhancement of high-affinity choline uptakeJournal of Neural Transmission, 2008 · PMID 18461273
  4. Subsequent exposure to the choline uptake enhancer MKC-231 antagonizes phencyclidine-induced behavioral deficits and reduction in septal cholinergic neurons in ratsEuropean Neuropsychopharmacology, 2007 · PMID 17467960
  5. Effect of MKC-231 on spatial learning retentionPharmacol Biochem Behav, 1999 · PMID 10400478
  6. MKC-231, a choline uptake enhancer, activates the cholinergic nervous systemJ Pharmacol Exp Ther, 1997 · PMID 9225290
  7. Effects of MKC-231 on high-affinity choline uptake in the hippocampusJpn J Pharmacol, 1996 · PMID 8799197
  8. Effect 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 ratsArzneimittelforschung, 1996 · PMID 8740080
  9. MKC-231, a choline uptake enhancer: effect on recovery from AF64A-induced learning impairmentJ Neural Transm, 1994 · PMID 8825012
  10. MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in miceJournal of Neural Transmission - General Section, 1994 · PMID 7710736