Aniracetam

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Aniracetam
Aniracetam2.svg
Aniracetam3d.png
Systematic (IUPAC) name
1-[(4-methoxybenzoyl)]-2-pyrrolidinone
Clinical data
Trade names Ampamet, Memodrin, Pergamid
AHFS/Drugs.com International Drug Names
Legal status
  • Unscheduled
Routes of
administration		 Oral
Pharmacokinetic data
Biological half-life 1-2.5 hours
Identifiers
CAS Number 72432-10-1 N
ATC code N06BX11 (WHO)
PubChem CID: 2196
IUPHAR/BPS 4133
DrugBank DB04599 YesY
ChemSpider 2111 YesY
UNII 5L16LKN964 YesY
KEGG D01883 YesY
ChEBI CHEBI:47943 YesY
ChEMBL CHEMBL36994 YesY
Chemical data
Formula C12H13NO3
Molecular mass 219.237 g/mol
  • 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 YesY
  • Key:ZXNRTKGTQJPIJK-UHFFFAOYSA-N YesY
 NYesY (what is this?)  (verify)

Aniracetam (Draganon, Sarpul, Ampamet, Memodrin, Referan), also known as N-anisoyl-2-pyrrolidinone, is an ampakine nootropic of the racetam chemical class purported to be considerably more potent than piracetam. It is lipid-soluble and has possible cognition-enhancing effects. It has been tested in animals extensively, Alzheimer's patients, and temporarily impaired healthy subjects. It has shown potential as an anxiolytic in three clinical animal models. It is sold in Europe as a prescription drug,[1] but it is not approved by the Food and Drug Administration for use in the United States.

Pharmacology

Aniracetam has also been shown to positively modulate the AMPA receptor[2] and was used as the parent compound to derive a class of drugs known as the ampakines that are being investigated as nootropics and neuroprotective drugs for the treatment of Alzheimer's disease and other neurodegenerative conditions.[3]

After a confirmed test of the anxiolytic efficacy in a mouse model, haloperidol, mecamylamine, and ketanserin were applied to determine the pathways aniracetam depends on to exert its anti-anxiety effects. Haloperidol completely reversed the anxiolytic effects, and mecamylamine and ketanserin nearly completely reversed the effects. This shows that aniracetam's anxiolytic mechanism is possibly mediated through D2, nACh, or 5-HT2A receptor activity.[4]

The main metabolite of aniracetam (70-80%), N-anisoyl-GABA, reproduces many of the effects of aniracetam.[5][6] 2-Pyrrolidinone and p-anisilic acid are additional metabolites of the drug (20-30%), both of which are also active.[6]

Synthesis

The drug was first made in the 1970s by Hoffmann-La Roche.[7][full citation needed][8][full citation needed] Synthesis can be accomplished by reacting 2-pyrrolidone with anisoyl chloride in the presence of triethylamine.[9]

Aniracetam synthesis 01.svg

Alternatively, gamma-aminobutyric acid can react with anisoyl chloride. Ring closure can be accomplished in the presence of thionyl chloride.[9]

Aniracetam synthesis 02.svg

Pharmacokinetics

When ingested orally aniracetam is quickly broken down via first pass hepatic metabolism. The primary metabolites of aniracetam are N-anisoyl-GABA, 2-pyrrolidone, and anisic acid.[10] 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 recreational usage of the drug. These two plasma species may be measured by liquid chromatography-mass spectrometry.[11][12][13]

See also

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ US 6730677, "Benzofurazan compounds which enhance AMPA receptor activity" 
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ 6.0 6.1 Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Patent EP 5 143 Hoffmann-La Roche 1978
  8. ↑ Patent EP 44 088 Hoffmann-La Roche 1978
  9. ↑ 9.0 9.1 A. Kleemann, J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications, 4. Auflage, Thieme 2001, ISBN 3-13-115134-X.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Cai S, Wang L. Determination of aniracetam's main metabolite, N-anisoyl-GABA, in human plasma by LC-MS/MS and its application to a pharmacokinetic study. J. Chromatogr. B 897: 50-54, 2012.
  12. ↑ Zhang J, Liang J, Tian Y, et al. Sensitive and selective liquid chromatography-tandem mass spectrometry method for the quantification of aniracetam in human plasma. J. Chromatogr. B 858: 129-134, 2007.
  13. ↑ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 10th edition, Biomedical Publications, Seal Beach, CA, 2014, p. 142-143.
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