Coluracetam

Coluracetam (INN) (code name BCI-540; formerly MKC-231) is a nootropic agent of the racetam family.[1] It was initially developed and tested by the Mitsubishi Tanabe Pharma Corporation for Alzheimer's disease. After the drug failed to reach endpoints in its clinical trials it was in-licensed by BrainCells Inc for investigations into major depressive disorder (MDD), which was preceded by being awarded a "Qualifying Therapeutic Discovery Program Grant" by the state of California.[2] Findings from phase IIa clinical trials have suggested that it would be a potential medication for comorbid MDD with generalized anxiety disorder (GAD).[3] BrainCells Inc is currently out-licensing the drug for this purpose.[4] It may also have potential use in prevention and treatment of ischemic retinopathy and retinal and optic nerve injury.

Coluracetam
Clinical data
ATC code
  • None
Identifiers
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC19H23N3O3
Molar mass341.404 g/mol g·mol−1
3D model (JSmol)

Coluracetam has been shown to reverse the loss of choline acetyltransferase production in the medial septal nucleus of rats exposed to phencyclidine (PCP), and is considered a potential therapeutic drug for schizophrenia.[5]

Mechanism of action

Coluracetam enhances high-affinity choline uptake (HACU),[6] which is the rate-limiting step of acetylcholine (ACh) synthesis. Studies have shown coluracetam to improve learning impairment on a single oral dose given to rats which have been exposed to cholinergic neurotoxins. Subsequent studies have shown that it may induce long-lasting procognitive effects in cholinergic neurotoxin-treated rats by changing the choline transporter regulation system.[7]

See also

References
  1. Bessho, T; Takashina, K; Tabata, R; Ohshima, C; Chaki, H; Yamabe, H; Egawa, M; Tobe, A; Saito, K (1996). "Effect of the novel high affinity choline uptake enhancer 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro2,3-b quinolin-4-yl)acetoamide on deficits of water maze learning in rats". Arzneimittel-Forschung. 46 (4): 369–73. PMID 8740080.
  2. Qualifying Therapeutic Discovery Project Grants for the State of California, IRS.gov.
  3. BrainCells Inc. Announces Results From Exploratory Phase 2a Trial of BCI-540 Archived November 21, 2011, at the Wayback Machine
  4. [Pipeline,BCI-540], BCI-540 (coluracetam).
  5. Shirayama, Y; Yamamoto, A; Nishimura, T; Katayama, S; Kawahara, R (2007). "Subsequent exposure to the choline uptake enhancer MKC-231 antagonizes phencyclidine-induced behavioral deficits and reduction in septal cholinergic neurons in rats". European Neuropsychopharmacology. 17 (9): 616–26. doi:10.1016/j.euroneuro.2007.02.011. PMID 17467960.
  6. S. Murai; et al. (1994). "MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice". Journal of Neural Transmission. 98 (1): 1–13. doi:10.1007/BF01277590. PMID 7710736.
  7. Bessho, T; Takashina, K; Eguchi, J; Komatsu, T; Saito, K (Jul 2008). "MKC-231, a choline-uptake enhancer: long-lasting cognitive improvement after repeated administration in AF64A-treated rats". Journal of Neural Transmission. 115 (7): 1019–25. doi:10.1007/s00702-008-0053-4. PMID 18461272.
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