Aniracetam

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Aniracetam
Aniracetam.svg
Aniracetam3d.png
Clinical data
Trade namesAmpamet, Memodrin, Pergamid
AHFS/Drugs.comInternational Drug Names
Routes of
administration
By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: Not approved
  • In general: unscheduled
Pharmacokinetic data
Elimination half-life1–2.5 hours
Identifiers
  • 1-[(4-Methoxybenzoyl)]-2-pyrrolidinone
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.108.230 Edit this at Wikidata
Chemical and physical data
FormulaC12H13NO3
Molar mass219.240 g·mol−1
3D model (JSmol)
  • O=C2N(C(=O)c1ccc(OC)cc1)CCC2
  • InChI=1S/C12H13NO3/c1-16-10-6-4-9(5-7-10)12(15)13-8-2-3-11(13)14/h4-7H,2-3,8H2,1H3 checkY
  • Key:ZXNRTKGTQJPIJK-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Aniracetam (brand names Draganon, Sarpul, Ampamet, Memodrin, Referan), also known as N-anisoyl-2-pyrrolidinone, is a racetam which is sold in Europe as a prescription drug. It is not approved by the Food and Drug Administration for use in the United States as a prescription medication or dietary supplement.[1][2] Despite the FDA's lack of approval, the drug is readily available over-the-counter in the US as a dietary supplement.[1]

Pharmacology[edit]

Aniracetam has been shown to positively modulate the AMPA receptor.[3]

When ingested orally aniracetam is quickly broken down via first pass hepatic metabolism. The primary metabolites of aniracetam are N-anisoyl-GABA, (70–80%), 2-Pyrrolidinone and p-anisic acid (20–30%).[4][5][6]

Plasma concentrations are generally in the 5–15 μg/L range for aniracetam and 5–15 mg/L range for N-anisoyl-GABA, a pharmacologically-active metabolite, during the first few hours after oral administration of the drug. These two plasma species may be measured by liquid chromatography-mass spectrometry.[7][8][9]

Synthesis[edit]

The drug was first made in the 1970s by Hoffmann-La Roche.[10][11] Synthesis can be accomplished by reacting 2-pyrrolidone with anisoyl chloride in the presence of triethylamine.[12]

Aniracetam synthesis 01.svg

Alternatively, gamma-aminobutyric acid can react with anisoyl chloride. Ring closure can be accomplished in the presence of thionyl chloride.[12]

Aniracetam synthesis 02.svg

Legality[edit]

Australia[edit]

Aniracetam is a schedule 4 substance in Australia under the Poisons Standard (February 2020).[13] 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." [13]

See also[edit]

References[edit]

  1. ^ a b Malykh AG, Sadaie MR (February 2010). "Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders". Drugs. 70 (3): 287–312. doi:10.2165/11319230-000000000-00000. PMID 20166767. S2CID 12176745.
  2. ^ Cohen, Pieter A.; Avula, Bharathi; Wang, Yan Hong; Zakharevich, Igor; Khan, Ikhlas (23 September 2020). "Five unapproved drugs found in cognitive enhancement supplements". Neurology: Clinical Practice: 10.1212/CPJ.0000000000000960. doi:10.1212/CPJ.0000000000000960.
  3. ^ Ito I, Tanabe S, Kohda A, Sugiyama H (May 1990). "Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam". The Journal of Physiology. 424: 533–43. doi:10.1113/jphysiol.1990.sp018081. PMC 1189827. PMID 1975272.
  4. ^ Lee CR, Benfield P (March 1994). "Aniracetam. An overview of its pharmacodynamic and pharmacokinetic properties, and a review of its therapeutic potential in senile cognitive disorders". Drugs & Aging. 4 (3): 257–73. doi:10.2165/00002512-199404030-00007. PMID 8199398.
  5. ^ Action A (22 July 2013). Schizophrenia: New Insights for the Healthcare Professional. ScholarlyEditions. pp. 152–. ISBN 978-1-4816-6196-6.
  6. ^ Testa B, Mayer JM (1 August 2003). Hydrolysis in Drug and Prodrug Metabolism. John Wiley & Sons. pp. 109–. ISBN 978-3-906390-25-3.
  7. ^ Cai S, Wang L (May 2012). "Determination of aniracetam's main metabolite, N-anisoyl-GABA, in human plasma by LC-MS/MS and its application to a pharmacokinetic study". Journal of Chromatography B. 897: 50–4. doi:10.1016/j.jchromb.2012.04.007. PMID 22552003.
  8. ^ Zhang J, Liang J, Tian Y, Zhang Z, Chen Y (October 2007). "Sensitive and selective liquid chromatography-tandem mass spectrometry method for the quantification of aniracetam in human plasma". Journal of Chromatography B. 858 (1–2): 129–34. doi:10.1016/j.jchromb.2007.08.010. PMID 17826366.
  9. ^ Baselt RC (2014). Disposition of Toxic Drugs and Chemicals in Man (10th ed.). Seal Beach, CA: Biomedical Publications. pp. 142–143. ISBN 978-0-9626523-9-4.
  10. ^ EP application 44088, Kyburz E, Aschwanden W, "p-Methoxy-benzoyl derivatives", published 9 February 1979, assigned to Hoffmann-La Roche 
  11. ^ EP 5143, Kyburz E, Aschwanden W, "1-Benzoyl-2-pyrrolidinone derivative, processes for its preparation and medicaments containing it.", published 9 February 1979, assigned to Hoffmann-La Roche 
  12. ^ a b Kleemann A, Engels J, Kutscher B, Reichert D (2001). Pharmaceutical substances: syntheses, patents, applications (4th ed.). Stuttgart: Thieme. ISBN 978-3-13-558404-1.
  13. ^ a b Poisons Standard February 2020. comlaw.gov.au