Coluracetam

2024-07-28T04:22:26Z

2001:5A8:429D:5E00:5C23:9847:DAA3:C1EB:

{{Short description|Chemical compound}}
{{Drugbox
| IUPAC_name = ''N''-(2,3-Dimethyl-5,6,7,8-tetrahydrofuro[2,3-''b'']quinolin-4-yl)-2-(2-oxo-1-pyrrolidinyl)acetamide
| image = Coluracetam.svg
| image2 = Coluracetam3d.png
| CAS_number = 135463-81-9
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = V6FL6O5GR7
| ATC_prefix = None
| ATC_suffix =
| PubChem = 214346
| DrugBank =
| ChemSpiderID = 185836
| chemical_formula =
| C=19 | H=23 | N=3 | O=3
| smiles = Cc1c(oc2c1c(c3c(n2)CCCC3)NC(=O)CN4CCCC4=O)C
| StdInChI = 1S/C19H23N3O3/c1-11-12(2)25-19-17(11)18(13-6-3-4-7-14(13)20-19)21-15(23)10-22-9-5-8-16(22)24/h3-10H2,1-2H3,(H,20,21,23)
| StdInChIKey = PSPGQHXMUKWNDI-UHFFFAOYSA-N
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
| pregnancy_AU = 
| pregnancy_US = 
| pregnancy_category=
| legal_AU = S4
| legal_CA = 
| legal_UK = 
| legal_US = Not FDA approved
| legal_status =
| routes_of_administration =
}}

'''Coluracetam''' ([[International Nonproprietary Name|INN]]; development code '''BCI-540'''; formerly '''MKC-231''') is a purported [[nootropic]] [[drug|agent]] of the [[racetam]] family.<ref>{{cite journal | vauthors = Bessho T, Takashina K, Tabata R, Ohshima C, Chaki H, Yamabe H, Egawa M, Tobe A, Saito K | display-authors = 6 | title = Effect of the novel high affinity choline uptake enhancer 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b] quinolin-4-yl)acetoamide on deficits of water maze learning in rats | journal = Arzneimittel-Forschung | volume = 46 | issue = 4 | pages = 369–73 | date = April 1996 | pmid = 8740080 }}</ref> It contains a chemical group that is a [[bioisostere]] of the [[Tacrine|9-amino-tetrahydroacridine]] family. 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.<ref name="CAgrants">[https://www.irs.gov/businesses/small/article/0,,id=228970,00.html Qualifying Therapeutic Discovery Project Grants for the State of California], IRS.gov.</ref> Findings from [[Phases of clinical research#Phase II|phase IIa]] [[clinical trial]]s have suggested that it would be a potential medication for [[comorbidity|comorbid]] MDD with [[generalized anxiety disorder]] (GAD).<ref name="PR-06142010">[http://www.braincellsinc.com/wp-content/uploads/2010/06/BCI-PR-06142010.pdf BrainCells Inc. Announces Results From Exploratory Phase 2a Trial of BCI-540] {{webarchive |url=https://web.archive.org/web/20130203023248/http://www.braincellsinc.com/wp-content/uploads/2010/06/BCI-PR-06142010.pdf }}</ref> BrainCells Inc is currently{{when|date=January 2015}} out-licensing the drug for this purpose.<ref name="BCI-540">[http://www.braincellsinc.com/pipeline/bci-540 BCI-540 (coluracetam) | BrainCells] {{webarchive |url=https://web.archive.org/web/20120831142254/http://www.braincellsinc.com:80/pipeline/bci-540 }}</ref> It may also have potential use in prevention and treatment of [[ischemia|ischemic]] [[retinopathy]] and [[retina]]l and [[optic nerve]] injury.{{medcn|date=January 2015}}

Coluracetam has been shown to reverse the loss of [[choline acetyltransferase]] production in the [[medial septal nucleus]] of rats exposed to [[PCP (drug)|phencyclidine]] (PCP), and is considered a potential therapeutic drug for [[schizophrenia]].<ref>{{cite journal | vauthors = Shirayama Y, Yamamoto A, Nishimura T, Katayama S, Kawahara R | title = Subsequent exposure to the choline uptake enhancer MKC-231 antagonizes phencyclidine-induced behavioral deficits and reduction in septal cholinergic neurons in rats | journal = European Neuropsychopharmacology | volume = 17 | issue = 9 | pages = 616–26 | date = September 2007 | pmid = 17467960 | doi = 10.1016/j.euroneuro.2007.02.011 | s2cid = 22967684 }}</ref>

==Mechanism of action==
Coluracetam enhances high-affinity [[choline]] [[reuptake|uptake]] (HACU),<ref>{{cite journal | vauthors = Murai S, Saito H, Abe E, Masuda Y, Odashima J, Itoh T | title = MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice | journal = Journal of Neural Transmission. General Section | volume = 98 | issue = 1 | pages = 1–13 | year = 1994 | pmid = 7710736 | doi = 10.1007/BF01277590 | s2cid = 23321953 }}</ref> which is the rate-limiting step of acetylcholine (ACh) [[biosynthesis|synthesis]]. Studies have shown coluracetam to improve [[learning impairment]] on a single oral dose given to rats which have been exposed to cholinergic [[neurotoxin]]s. Subsequent studies have shown that it may induce long-lasting [[nootropic|procognitive]] effects in [[cholinergic]] neurotoxin-treated rats by changing the [[choline transporter]] regulation system.<ref name="pmid18461272">{{cite journal | vauthors = Bessho T, Takashina K, Eguchi J, Komatsu T, Saito K | title = MKC-231, a choline-uptake enhancer: (1) long-lasting cognitive improvement after repeated administration in AF64A-treated rats | journal = Journal of Neural Transmission | volume = 115 | issue = 7 | pages = 1019–25 | date = July 2008 | pmid = 18461272 | doi = 10.1007/s00702-008-0053-4 | s2cid = 20201642 }}</ref>

== Legality ==
=== Australia ===
Coluracetam is a schedule 4 substance in Australia under the [[Standard for the Uniform Scheduling of Medicines and Poisons|Poisons Standard (February 2020)]].<ref name="Poisons Stanrard">[https://www.legislation.gov.au/Details/F2020C00148 Poisons Standard February 2020]. comlaw.gov.au</ref> A schedule 4 substance is classified as "Prescription Only Medicine, or Prescription Animal Remedy – Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription."<ref name="Poisons Stanrard" />

== See also ==
* [[Piracetam]]
* [[Tricyanoaminopropene]]

== References ==
{{Reflist|2}}

{{Racetams}}
{{Acetylcholine metabolism and transport modulators}}

[[Category:Racetams]]
[[Category:Acetamides]]
[[Category:Furans]]
[[Category:Experimental drugs]]

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Coluracetam