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]
Medical uses
Aniracetam has been used to treat
dementia following
stroke and in
Alzheimer's disease.[5] It has undergone a number of experiments in rodents; in a 1982 experiment on rats and mice it was found to have a variety of
psychoactive effects, improving learning and memory that was otherwise impaired experimentally.[6] It has been identified as a
nootropic drug due to these memory effects.[7] A 2001 study reported that in mice it has modest effects similar to an
anxiolytic.[8]
Pharmacology
Aniracetam has been shown to positively modulate the
AMPA receptor.[9]
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][10][11] 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 aniracetam in rats.[12] Further work in rats suggests that N-anisoyl-GABA may contribute more to increasing acetylcholine release than aniracetam itself.[13] 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.[12] The authors of the aforementioned study hypothesized that the metabolites work by increasing levels of dopamine and by stimulating the nicotinic acetylcholine receptors.[12]
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.[14][15][16]
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.[20]
Australia
Aniracetam is a schedule 4 substance in Australia under the
Poisons Standard (February 2020).[21] 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."[21]
^
abLee 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.
PMID8199398.
^Cumin R, Bandle EF, Gamzu E, Haefely WE (October 1982). "Effects of the novel compound aniracetam (Ro 13-5057) upon impaired learning and memory in rodents". Psychopharmacology. 78 (2): 104–111.
doi:
10.1007/bf00432244.
PMID6817363.
S2CID21784298.
^Nakamura K, Kurasawa M (May 2001). "Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism". European Journal of Pharmacology. 420 (1): 33–43.
doi:
10.1016/s0014-2999(01)01005-6.
PMID11412837.
^
abcNakamura 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.
PMID11702095.
S2CID26390117.
^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.
PMID10699452.
S2CID44976290.
^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.
PMID22552003.
^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.
PMID17826366.
^Baselt RC (2014). Disposition of Toxic Drugs and Chemicals in Man (10th ed.). Seal Beach, CA: Biomedical Publications. pp. 142–143.
ISBN978-0-9626523-9-4.
^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
^
abKleemann A, Engels J, Kutscher B, Reichert D (2001). Pharmaceutical substances: syntheses, patents, applications (4th ed.). Stuttgart: Thieme.
ISBN978-3-13-558404-1.