Coluracetam (MKC-231, BCI-540) is a synthetic racetam developed by Mitsubishi Tanabe Pharma as an Alzheimer's disease candidate, subsequently in-licensed by BrainCells Inc. and investigated in major depressive disorder.
Mechanism of Action
The only known pharmacological agent that specifically enhances HACU (High-Affinity Choline Uptake) — sodium-dependent choline transport via the CHT1 transporter, the rate-limiting step in acetylcholine synthesis. Incubation with hippocampal synaptosomes from AF64A-lesioned rats (10⁻¹⁰–10⁻⁶ mol/L) significantly increases HACU Vmax without altering Km. Critically: no effect is observed in synaptosomes from intact rats — the mechanism is activated only under conditions of cholinergic deficit. Does not affect AChE activity, M1 (pirenzepine) or M2 (QNB) muscarinic receptor binding — thus is neither an AChE inhibitor nor a muscarinic receptor agonist/antagonist.
Preclinical Data
Improved Morris water maze learning in AF64A-treated rats. Chronic administration is more effective than acute dosing: in the chronic regimen, outperforms tacrine (THA) at equivalent doses without its side effects (tremor, salivation, hypothermia).
Clinical Data
Phase 2a (BrainCells Inc.) in patients with major depressive disorder comorbid with generalized anxiety disorder — demonstrated positive effects on depressive and anxiety symptoms.
BIOLABCHEMICALS