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]
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| Trade names | Ampamet, Memodrin, Pergamid |
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| Routes of administration | By mouth |
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| Elimination half-life | 0.5 hours[1][2] |
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| ECHA InfoCard | 100.108.230 |
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| Formula | C12H13NO3 |
| Molar mass | 219.240 g·mol−1 |
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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]
Synthesis
The drug was first made in the 1970s by Hoffmann-La Roche.[17][18] Synthesis can be accomplished by reacting 2-pyrrolidone with anisoyl chloride in the presence of triethylamine.[19]
Alternatively, gamma-aminobutyric acid can react with anisoyl chloride. Ring closure can be accomplished in the presence of thionyl chloride.[19]
Legality
Europe
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]