Neuroscience Research Compound · For laboratory research use only
Also known as MKC-231, BCI-540
Coluracetam (MKC-231; N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl)-2-(2-oxopyrrolidin-1-yl)acetamide) is a synthetic compound that carries the 2-oxopyrrolidine acetamide group of the racetam class on a tetrahydrofuroquinoline ring system6. It has been characterised in the research literature as an enhancer of high-affinity choline uptake (HACU), the rate-limiting step of acetylcholine synthesis4.
Published research is preclinical. Most studies used rodents treated with the cholinergic neurotoxin ethylcholine aziridinium ion (AF64A), with further work in a phencyclidine model in rats, cultured cortical neurons and a rat visceral pain model1,2,3,4,5,6,7.
As described in the research literature
As described in the research literature, treatment of AF64A-lesioned rats with MKC-231 increased the Vmax of HACU and the Bmax of [3H]hemicholinium-3 binding in hippocampal synaptosomes. Radioligand binding and Biacore analysis showed affinity for the cloned high-affinity choline transporter CHT1, and the authors proposed that the compound affects CHT1 trafficking, increasing the number of transporters at the synaptic membrane4.
In hippocampal synaptosomes and slices from AF64A-treated rats, MKC-231 reversed reductions in HACU and in potassium-evoked acetylcholine release, and in vivo microdialysis examined basal acetylcholine concentrations3. In repeated-exposure rat studies, changes in HACU followed the same time course as behavioural measures, including at time points when the compound was no longer detected in brain, which the authors linked to changes in the regulation of the choline transporter2.
In cortical cultures from fetal rats, protection against glutamate cytotoxicity was examined; MKC-231 reduced cytotoxicity induced by the calcium ionophore ionomycin but not by a nitric oxide donor, pointing to suppression of nitric oxide formation triggered by calcium influx6.
What published studies have examined
Mice and rats lesioned with AF64A were used to examine working memory in a delayed non-matching to sample T-maze task1 and spatial learning in the water maze2, together with hippocampal acetylcholine content, HACU and acetylcholine release1,2,3.
Kinetic studies of HACU, hemicholinium-3 binding, [3H]-MKC-231 binding and surface plasmon resonance with cloned CHT1 were used to examine the mode of action at the high-affinity choline transporter4.
Sources [4]
In rats previously exposed to repeated phencyclidine, subsequent subchronic MKC-231 was examined for effects on locomotor responses to drug challenges, novel object recognition, choline acetyltransferase-positive cells in the medial septum and dynorphin A expression in the ventral striatum5.
Sources [5]
Glutamate, ionomycin and nitric oxide donor cytotoxicity were compared in cultured rat cortical neurons6. In a rat model of chronic water avoidance stress, colonic CHT1 expression, acetylcholine production and visceral sensitivity to colorectal distension were examined with MKC-231 as a pharmacological tool7.
MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice.
Murai S, Saito H, Abe E, et al. Journal of Neural Transmission. General Section, 1994.
MKC-231, a choline-uptake enhancer: (1) long-lasting cognitive improvement after repeated administration in AF64A-treated rats.
Bessho T, Takashina K, Eguchi J, et al. Journal of Neural Transmission, 2008.
MKC-231, a choline uptake enhancer: (2) Effect on synthesis and release of acetylcholine in AF64A-treated rats.
Takashina K, Bessho T, Mori R, et al. Journal of Neural Transmission, 2008.
MKC-231, a choline uptake enhancer: (3) Mode of action of MKC-231 in the enhancement of high-affinity choline uptake.
Takashina K, Bessho T, Mori R, et al. Journal of Neural Transmission, 2008.
Subsequent exposure to the choline uptake enhancer MKC-231 antagonizes phencyclidine-induced behavioral deficits and reduction in septal cholinergic neurons in rats.
Shirayama Y, Yamamoto A, Nishimura T, et al. European Neuropsychopharmacology, 2007.
Protective effect of MKC-231, a novel high affinity choline uptake enhancer, on glutamate cytotoxicity in cultured cortical neurons.
Akaike A, Maeda T, Kaneko S, et al. Japanese Journal of Pharmacology, 1998.
Upregulation of the high-affinity choline transporter in colon relieves stress-induced hyperalgesia.
Lin MJ, Yu BP Journal of Pain Research, 2018.
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.