Coluracetam

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Coluracetam
Coluracetam.svg
Coluracetam3d.png
Systematic (IUPAC) name
N-(2,3-Dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl)-2-(2-oxo-1-pyrrolidinyl)acetamide
Clinical data
Identifiers
135463-81-9
None
PubChem CID 214346
ChemSpider 185836
Chemical data
Formula C19H23N3O3
341.404 g/mol

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][dead link] BrainCells Inc is currently[when?] out-licensing the drug for this purpose.[4][full citation needed] It may also have potential use in prevention and treatment of ischemic retinopathy and retinal and optic nerve injury.[medical citation needed]

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[edit]

Coluracetam enhances high-affinity choline uptake,[citation needed] 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.[6]

See also[edit]

References[edit]

  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
  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.  edit
  6. ^ "MKC-231, a choline-uptake enhancer: long-lasting cognitive improvement after repeated administration in AF64A-treated rats". Journal of Neural Transmission 115: 1019–25. Jul 2008. doi:10.1007/s00702-008-0053-4. PMID 18461272.