Aniracetam
Aniracetam, 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. Despite the FDA's lack of approval, the drug is readily available over-the-counter in misbranded dietary supplements.
Medical uses
Aniracetam has been used to treat dementia following stroke and in Alzheimer's disease. Results from human clinical trials were published in 1991 and in 2011.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 of psychoactive effects, improving learning and memory that was otherwise impaired experimentally. It has been identified as a nootropic drug due to these memory effects. A 2001 study reported that in mice it has modest effects similar to an anxiolytic.
Pharmacology
Aniracetam has been shown to positively modulate the AMPA receptor.When ingested orally aniracetam is quickly broken down via first pass hepatic metabolism. The primary metabolites of aniracetam are N-anisoyl-GABA,, 2-Pyrrolidinone and p-anisic acid. 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. Further work in rats suggests that N-anisoyl-GABA may contribute more to increasing acetylcholine release than aniracetam itself. 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. The authors of the aforementioned study hypothesized that the metabolites work by increasing levels of dopamine and by stimulating the nicotinic acetylcholine receptors.
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.
Synthesis
The drug was first made in the 1970s by Hoffmann-La Roche. Synthesis can be accomplished by reacting 2-pyrrolidone with anisoyl chloride in the presence of triethylamine.Image:Aniracetam synthesis 01.svg|class=skin-invert-image|480px
Alternatively, gamma-aminobutyric acid can react with anisoyl chloride. Ring closure can be accomplished in the presence of thionyl chloride.
Image:Aniracetam synthesis 02.svg|class=skin-invert-image|500px