Aniracetam

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.[3][4] Despite the FDA's lack of approval, the drug is readily available over-the-counter in misbranded dietary supplements.[3]

Aniracetam
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: Unapproved "New Drug" (as defined by 21 U.S. Code § 321(p)(1)). Use in dietary supplements, food, or medicine is unlawful; otherwise uncontrolled.
Pharmacokinetic data
Elimination half-life0.5 hours[1][2]
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
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)

Pharmacology

Aniracetam has been shown to positively modulate the AMPA receptor.[5]

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%).[2][6][7] There is some preliminary research suggesting that N-anisoyl-GABA and to a lesser degree p-ansic acid may contribute to the stimulatory effects of aniracetamin in rats.[8] Further work in rats suggets that N-anisoyl-GABA may contribute more to increasing acetylcholine release than aniracetam itself.[9] For instance, a study using the forced swim test in rats found that the two metabolites 2-pyrrolidinone and N-anisoyl-GABA alone yielded similar anti-depressant effects as aniracetam itself.[8] The authors of the aforementioned study hypothesized that the metabolites work by increasing levels of dopamine and by stimulating the nicotinic acetylcholine receptors.[8]

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.[10][11][12]

Synthesis

The drug was first made in the 1970s by Hoffmann-La Roche.[13][14] Synthesis can be accomplished by reacting 2-pyrrolidone with anisoyl chloride in the presence of triethylamine.[15]

Alternatively, gamma-aminobutyric acid can react with anisoyl chloride. Ring closure can be accomplished in the presence of thionyl chloride.[15]

Legality

Europe

Aniracetam is available by prescription in Greece (brand names Memodrin and Referan) and Italy (brand name Ampamet), where it is indicated for mental function disorders.[16]

Australia

Aniracetam is a schedule 4 substance in Australia under the Poisons Standard (February 2020).[17] 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."[17]

See also

References
  1. Roncari G (June 1993). "Human Pharmacokinetics of Aniracetam". Drug Investigation. 5 (S1): 68–72. doi:10.1007/BF03258428. S2CID 96775295.
  2. 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): 257–273. doi:10.2165/00002512-199404030-00007. PMID 8199398.
  3. 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.
  4. Cohen PA, Avula B, Wang YH, Zakharevich I, Khan I (June 2021). "Five Unapproved Drugs Found in Cognitive Enhancement Supplements". Neurology. Clinical Practice. 11 (3): e303–e307. doi:10.1212/CPJ.0000000000000960. PMC 8382366. PMID 34484905.
  5. 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: 533–543. doi:10.1113/jphysiol.1990.sp018081. PMC 1189827. PMID 1975272.
  6. Action A (22 July 2013). Schizophrenia: New Insights for the Healthcare Professional. ScholarlyEditions. pp. 152–. ISBN 978-1-4816-6196-6.
  7. Testa B, Mayer JM (1 August 2003). Hydrolysis in Drug and Prodrug Metabolism. John Wiley & Sons. pp. 109–. ISBN 978-3-906390-25-3.
  8. Nakamura K, Tanaka Y (November 2001). "Antidepressant-like effects of aniracetam in aged rats and its mode of action". Psychopharmacology. 158 (2): 205–212. doi:10.1007/s002130100849. PMID 11702095.
  9. Shirane M, Nakamura K (March 2000). "Group II metabotropic glutamate receptors are a common target of N-anisoyl-GABA and 1S,3R-ACPD in enhancing ACh release in the prefrontal cortex of freely moving SHRSP". Neuropharmacology. 39 (5): 866–872. doi:10.1016/s0028-3908(99)00271-3. PMID 10699452.
  10. 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, Analytical Technologies in the Biomedical and Life Sciences. 897: 50–54. doi:10.1016/j.jchromb.2012.04.007. PMID 22552003.
  11. 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, Analytical Technologies in the Biomedical and Life Sciences. 858 (1–2): 129–134. doi:10.1016/j.jchromb.2007.08.010. PMID 17826366.
  12. 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.
  13. EP application 44088, Kyburz E, Aschwanden W, "p-Methoxy-benzoyl derivatives", published 9 February 1979, assigned to Hoffmann-La Roche
  14. 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
  15. Kleemann A, Engels J, Kutscher B, Reichert D (2001). Pharmaceutical substances: syntheses, patents, applications (4th ed.). Stuttgart: Thieme. ISBN 978-3-13-558404-1.
  16. "Classification Status of Racetams" (PDF). New Zealand Medicines and Medical Devices Safety Authority. Retrieved 5 February 2023.
  17. Poisons Standard February 2020. comlaw.gov.au
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