Coluracetam 135463-81-9 ≥98% Purity - Quality Powder from China Suppliers and Factory
Brief Introduction
Key Scientific Value & Findings
Unique Choline Uptake Enhancement Mechanism
Coluracetam is a new choline uptake enhancer. MKC-231 significantly increased high-affinity choline uptake when incubated with hippocampal synaptosomes of ethylcholine mustard aziridinium ion (AF64A)-treated rats, but not of normal rats. Studies show that MKC-231 increased the Vmax of HACU and Bmax of [3H]-HC-3 binding by 1.6 and 1.7-fold, respectively. In [3H]-MKC-231 binding and Biacore analysis, MKC-231 showed noticeable affinity for cloned high-affinity choline transporters (CHT1).
No Effect on Acetylcholinesterase or Receptors
MKC-231 did not affect AChE activity, [3H]-quinuclidinyl benzilate binding, or [3H]-pirenzepine binding, indicating its mechanism is completely distinct from acetylcholinesterase inhibitors or direct cholinergic agonists.
Persistent Improvement with Chronic Administration
In chronic experiments, MKC-231 (0.3, 1.0, or 3.0 mg/kg p.o., once daily for 11 days) significantly improved working memory deficits induced by AF64A in mice. Correct response rates in a delayed non-matching to sample task in a T-maze improved from 61.1% (AF64A+vehicle) to 86.1%, 85.0%, and 83.3% at doses of 0.3, 1.0, and 3.0 mg/kg, respectively. Acute single administration (same doses) did not significantly improve AF64A-induced working memory deficits.
Restoration of Hippocampal ACh Levels
Chronic oral administration of MKC-231 (0.3 and 1.0 mg/kg, once daily for 12 days) significantly reversed the depletion of hippocampal ACh content induced by AF64A in mice. ACh levels increased from 60.8% of control (AF64A+vehicle) to 84.4% and 75.5% of control at doses of 0.3 and 1.0 mg/kg, respectively. The effect at 3.0 mg/kg (65.0% of control) was not significant, indicating a bell-shaped dose-response curve. Acute oral administration of MKC-231 did not reverse AF64A-induced hippocampal ACh depletion.
Improvement of Water Maze Learning Deficits
Oral administration of MKC-231 (1-10 mg/kg) significantly improved learning deficits in the Morris water maze of AF64A-treated rats. Unlike high doses of tacrine, MKC-231 did not produce any significant side effects like tremor, salivation, or hypothermia.
Modulation of Glutamate and GABA Levels
Coluracetam also acts by increasing glutamate and GABA levels, neurotransmitters involved in learning and memory. Additionally, it increases the efficiency of signal transmission between neurons.