Aniracetam (brand namesDraganon,Sarpul,Ampamet,Memodrin,Referan), also known asN-anisoyl-2-pyrrolidinone, is aracetam which is sold in Europe as aprescription drug. It is not approved by theFood and Drug Administration for use in the United States as a prescription medication ordietary supplement.[3][4] Despite the FDA's lack of approval, the drug is readily available over-the-counter in misbranded dietary supplements.[3]
Aniracetam has been used to treatdementia followingstroke and inAlzheimer's disease.[5] Results from human clinical trials were published in 1991 (one multi-center placebo-controlled study and a follow-up) and in 2011 (one open-label study).[6]
It has undergone a larger number of experiments in rodents; in a 1982 experiment on rats and mice it was found to have a variety ofpsychoactive effects, improving learning and memory that was otherwise impaired experimentally.[7] It has been identified as anootropic drug due to these memory effects.[8] A 2001 study reported that in mice it has modest effects similar to ananxiolytic.[9]
Aniracetam has been shown to positively modulate theAMPA receptor.[10]
When ingested orally aniracetam is quickly broken down via first pass hepatic metabolism. The primary metabolites of aniracetam areN-anisoyl-GABA, (70–80%),2-Pyrrolidinone andp-anisic acid (20–30%).[2][11][12] 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.[13] Further work in rats suggests that N-anisoyl-GABA may contribute more to increasing acetylcholine release than aniracetam itself.[14] For instance, a study using theforced swim test in rats found that the two metabolites 2-pyrrolidinone and N-anisoyl-GABA alone yielded similar anti-depressant effects as aniracetam itself.[13] The authors of the aforementioned study hypothesized that the metabolites work by increasing levels of dopamine and by stimulating the nicotinic acetylcholine receptors.[13]
Plasma concentrations are generally in the 5–15μg/L range for aniracetam and 5–15 mg/L range forN-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.[15][16][17]
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.[21]
Aniracetam is a schedule 4 substance in Australia under thePoisons Standard (February 2020).[22] 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."[22]
^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.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.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.
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