Aniracetam

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Aniracetam
Aniracetam2.svg
Aniracetam3Dan.gif
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 Oral
Pharmacokinetic data
Half-life 1-2.5 hours
Identifiers
CAS number 72432-10-1 N
ATC code N06BX11
PubChem CID 2196
DrugBank DB04599
ChemSpider 2111 YesY
UNII 5L16LKN964 YesY
KEGG D01883 YesY
ChEBI CHEBI:47943 YesY
ChEMBL CHEMBL36994 YesY
Chemical data
Formula C12H13NO3 
Mol. mass 219.237 g/mol
 N (what is this?)  (verify)

Aniracetam (Draganon, Sarpul, Ampamet, Memodrin, Referan) 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[edit]

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 facilitated by D2, nACh, and 5-HT2A receptors.[2]

Aniracetam has also been shown to selectively modulate the AMPA receptor[3] 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.[4]

Synthesis[edit]

The drug was first made in the 1970s by Hoffmann-La Roche.[5][full citation needed][6][full citation needed] Synthesis can be accomplished by reacting 2-pyrrolidone with anisoyl chloride in the presence of triethylamine.[7]

Aniracetam synthesis 01.svg

Alternatively, gamma-aminobutyric acid can react with anisoyl chloride. Ring closure can be accomplished in the presence of thionyl chloride.[7]

Aniracetam synthesis 02.svg

Pharmacokinetics[edit]

Aniracetam is lipid soluble and is able to cross the blood brain barrier. The primary metabolites of aniracetam are N-anisoyl-GABA, 2-pyrrolidone, and anisic acid.[8]

See also[edit]

References[edit]

  1. ^ Malykh AG; Sadaie MR (Feb 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. 
  2. ^ Nakamura K; Kurasawa M (May 2001). "Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism". Eur J Pharmacol. (Kanagawa, Japan). 420 (1): 33–43. doi:10.1016/S0014-2999(01)01005-6. PMID 11412837. 
  3. ^ Ito et al.; Tanabe, S; Kohda, A; Sugiyama, H (1990). "Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam". J. Physiol. 424: 533–543. PMC 1189827. PMID 1975272. 
  4. ^ US 6730677, "Benzofurazan compounds which enhance AMPA receptor activity" 
  5. ^ Patent EP 5 143 Hoffmann-La Roche 1978
  6. ^ Patent EP 44 088 Hoffmann-La Roche 1978
  7. ^ a b A. Kleemann, J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications, 4. Auflage, Thieme 2001, ISBN 3-13-115134-X.
  8. ^ Lee, CR; Benfield, P (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.