Coluracetam

•Last Updated: September 28 2022

Coluracetam (MKC-231) is a racetam drug purported to be a cognitive enhancing drug. It is able to preserve choline uptake into neurons when they are otherwise impaired, but currently there is no evidence for inherent nootropic effects.

dosage

Coluracetam is most often used for

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Kamal Patel, MPH, MBA

Last Updated: September 28 2022

summary
Dosage information
Research breakdown
References

Summary

Coluracetam (MKC-231) is a synthetic racetam drug purported to be a nootropic compound. It does not have a large body of evidence investigating it, but the mechanisms of action (as well as structure) appear to be very distinct from other racetam compounds like Piracetam or Aniracetam.

Coluracetam appears to interact with a process known as high affinity choline uptake (HACU for short), which is the rate-limiting step of drawing choline into a neuron for synthesis into the neurotransmitter acetylcholine. Increasing the HACU rate appears to increase the activity of cholinergic neurons, so it is a desired target for cognitive enhancement.

Interventions in rats (as there is no human evidence currently) support the usage of coluracetam at very low oral doses to preserve HACU that is otherwise impaired by the use of research drugs that are known to impair HACU. The limited evidence looking at the inherent effects of coluracetam on the HACU of normal neurons has failed to find any significant interaction.

Coluracetam has also been noted to associate with choline transporters physically, but it is not known exactly what it does once associated.

Overall, there is currently insufficient evidence to support the usage of coluracetam for cognitive enhancement. Further studies are needed to see if it has a therapeutic role in instances where HACU may be impaired (such as Alzheimer's disease).

What else is Coluracetam known as?

Note that Coluracetam is also known as:

MKC-231
BCI-540
2-(2-oxypyrrolidin-1-yl)-N-(2 3-dimethyl-5 6 7 8-tetrahydrofuro(2 3-b)quinolin-4-yl)acetoamide

Dosage information

The animal research on coluracetam uses an oral dose of 300-3,000mcg/kg bodyweight, which is roughly translated into a human dose of 48-480mcg/kg or (for a 150lb person) 3.2-32.7mg overall.

It appears to have very rapid kinetics, with a peak in blood at around 30 minutes and on the decline within 3 hours. Due to this, supplementation may be time-dependent in relation to activity.

Research Breakdown

1

Sources and Structure

1.1

Sources

1.2

Structure

2

Pharmacology

2.1

Serum

2.2

Neurological

3

Neurology

3.1

Cholinergic Neurotransmission

3.2

Glutaminergic Neurotransmission

References

1.^Takashina K, Bessho T, Mori R, Kawai K, Eguchi J, Saito KMKC-231, a choline uptake enhancer: (3) Mode of action of MKC-231 in the enhancement of high-affinity choline uptakeJ Neural Transm.(2008 Jul)

2.^Bessho T, Takashina K, Eguchi J, Komatsu T, Saito KMKC-231, a choline-uptake enhancer: (1) long-lasting cognitive improvement after repeated administration in AF64A-treated ratsJ Neural Transm.(2008 Jul)

3.^Simon JR, Atweh S, Kuhar MJSodium-dependent high affinity choline uptake: a regulatory step in the synthesis of acetylcholineJ Neurochem.(1976 May)

4.^Yamamura HI, Snyder SHHigh affinity transport of choline into synaptosomes of rat brainJ Neurochem.(1973 Dec)

5.^Rodríguez-Puertas R, Pazos A, Zarranz JJ, Pascual JSelective cortical decrease of high-affinity choline uptake carrier in Alzheimer's disease: an autoradiographic study using 3H-hemicholinium-3J Neural Transm Park Dis Dement Sect.(1994)

6.^Rylett RJ, Ball MJ, Colhoun EHEvidence for high affinity choline transport in synaptosomes prepared from hippocampus and neocortex of patients with Alzheimer's diseaseBrain Res.(1983 Dec 19)

7.^Slotkin TA, Seidler FJ, Crain BJ, Bell JM, Bissette G, Nemeroff CBRegulatory changes in presynaptic cholinergic function assessed in rapid autopsy material from patients with Alzheimer disease: implications for etiology and therapyProc Natl Acad Sci U S A.(1990 Apr)

8.^Fisher A, Mantione CR, Abraham DJ, Hanin ILong-term central cholinergic hypofunction induced in mice by ethylcholine aziridinium ion (AF64A) in vivoJ Pharmacol Exp Ther.(1982 Jul)

9.^Takashina K, Bessho T, Mori R, Eguchi J, Saito KMKC-231, a choline uptake enhancer: (2) Effect on synthesis and release of acetylcholine in AF64A-treated ratsJ Neural Transm.(2008 Jul)

10.^Bessho T, Takashina K, Tabata R, Ohshima C, Chaki H, Yamabe H, Egawa M, Tobe A, Saito KEffect 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 Apr)

11.^Murai S, Saito H, Abe E, Masuda Y, Odashima J, Itoh TMKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in miceJ Neural Transm Gen Sect.(1994)

12.^Morris BJ, Cochran SM, Pratt JAPCP: from pharmacology to modelling schizophreniaCurr Opin Pharmacol.(2005 Feb)

13.^Shirayama Y, Yamamoto A, Nishimura T, Katayama S, Kawahara RSubsequent exposure to the choline uptake enhancer MKC-231 antagonizes phencyclidine-induced behavioral deficits and reduction in septal cholinergic neurons in ratsEur Neuropsychopharmacol.(2007 Sep)

14.^Akaike A, Maeda T, Kaneko S, Tamura YProtective effect of MKC-231, a novel high affinity choline uptake enhancer, on glutamate cytotoxicity in cultured cortical neuronsJpn J Pharmacol.(1998 Feb)

Primary Use