Aniracetam

Aniracetam
Clinical data
Trade names	Ampamet, Memodrin, Pergamid
AHFS/Drugs.com	International Drug Names
Routes of; administration	By mouth
ATC code	N06BX11 (WHO) ;
Legal status
Legal status	AU: Schedule 4 (Prescription Only) ; US: Not approved; In general: unscheduled;
Pharmacokinetic data
Elimination half-life	1–2.5 hours
Identifiers
	IUPAC name 1-[(4-Methoxybenzoyl)]-2-pyrrolidinone;
CAS Number	72432-10-1 ;
PubChem CID	2196;
IUPHAR/BPS	4133;
DrugBank	DB04599 ;
ChemSpider	2111 ;
UNII	5L16LKN964;
KEGG	D01883 ;
ChEBI	CHEBI:47943 ;
ChEMBL	ChEMBL36994 ;
CompTox Dashboard (EPA)	DTXSID5045128 ;
ECHA InfoCard	100.108.230
Chemical and physical data
Formula	C12H13NO3
Molar mass	219.240 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C2N(C(=O)c1ccc(OC)cc1)CCC2;
	InChI 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 ; Key:ZXNRTKGTQJPIJK-UHFFFAOYSA-N ;
	(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

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

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]

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

Australia

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]

References

^ ^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.
^ 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.
^ 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.
^ 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.
^ Action A (22 July 2013). Schizophrenia: New Insights for the Healthcare Professional. ScholarlyEditions. pp. 152–. ISBN 978-1-4816-6196-6.
^ Testa B, Mayer JM (1 August 2003). Hydrolysis in Drug and Prodrug Metabolism. John Wiley & Sons. pp. 109–. ISBN 978-3-906390-25-3.
^ 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.
^ 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.
^ 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.
^ EP application 44088, Kyburz E, Aschwanden W, "p-Methoxy-benzoyl derivatives", published 9 February 1979, assigned to Hoffmann-La Roche
^ 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
^ ^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.
^ ^a ^b Poisons Standard February 2020. comlaw.gov.au

[Neuro-1] 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.

[TestaMayer2003-6] Testa B, Mayer JM (1 August 2003). Hydrolysis in Drug and Prodrug Metabolism. John Wiley & Sons. pp. 109–. ISBN 978-3-906390-25-3.

[Cai_2012-7] 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

[Kleemann-12] Kleemann A, Engels J, Kutscher B, Reichert D (2001). Pharmaceutical substances: syntheses, patents, applications (4th ed.). Stuttgart: Thieme. ISBN 978-3-13-558404-1.

[Poisons_Stanrard-13] Poisons Standard February 2020. comlaw.gov.au

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