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Aniracetam is a nootropic and medication prescribed in the EU for the treatment of cognitive impairments. It is largely unscheduled and is sometimes sold as a diet supplement, often marketed for boosting productivity. It is used as a clinical treatment for stroke and dementia in Asia, including Japan (although it was discontinued after eight years of use due to apparent lack of efficacy demonstrated in a double-blind, placebo controlled clinical trial) [1].

Aniracetam acts as an enhancer of cholinergic reuptake in the brain. It acheives this effect by behaving as a positive allosteric modulator (PAM) of the AMPA receptors, as well as the metabotropic glutamate (mGlu) receptors. Due to its mechanism of action (AMPA receptors and mGlu receptors can influence production of serotonin and dopamine), aniracetam can also indirectly enhance the release of dopamine and serotonin in the amygdalal and hippocampal regions of the brain, and has been demonstrated to do so in rats [2]. Physiologically there is no toxicity associated with aniracetam usage in humans, and no cases of aniracetam fatalities are documented in the
literature, despite its fairly widespread usage as a prescription drug and a nootropic. It is not known to have any behavioral or psychoactive effects on its own.

Due to its mechanism of action largely depending on enhancing cholinergic neurotransmission, combining aniracetam with a choline supplement (or dietary source of choline) is usually recommended to improve its benefits. Additionally, due to its mGlu PAM effects, it enhances the excitatory neurotransmitter action of glutamate, which means that supplemented glutamate (or other dietary sources such as L-theanine, glutamine, aceglutamide, and pyroglutamic acid) may potentiate the effect of aniracetam as well (however, this is more speculative and less supported by research than the synergy between choline and aniracetam).

In one placebo controlled, multicentre clinical study conducted in 1994, aniracetam showed significant improvement over a 6-month course of treatment for "mild to moderate cognitive impairment fulfilling NINCDS-ADRDA criteria" arising from dementia or Alzheimer's. [3] No significant side effects associated with its usage were found in the treatment group, and the treatment had a high rate of tolerability among patients.

Another placebo-controlled, double blind clinical trial from 1991 found aniracetam (1500 mg/day) to be superior in efficacy to piracetam (2400 mg/day) over a 6-month course of treatment for elderly patients with MCI due to senile dementia and Alzheimer's. [4]

A more modern clinical trial in humans (2012, open-label, with no placebo control) for aniracetam found it to be effective for improving neuropsychological test scores in elderly patients with mild cognitive impairment (MCI) due to early-stage dementia, with significant improvements in emotional test scores [5]. Compared to acetylcholinesterase inhibitors (AChEIs such as galantamine, rivastigmine and donepezil), aniracetam performed significantly better in long term test scores, with major drops in cognitive ability appearing in the AChEI control group after 6-12 months of treatment. Additionally, aniracetam monotherapy significantly outperformed combined treatment with aniracetam and AChEIs. Not only this, but the combined treatment group also outperformed the long term test scores of those who received AChEI monotherapy, indicating aniracetam to be a better performer in the long-term treatment of Alzheimer's disease.

This compound is not for human consumption, and its sale is strictly intended for research purposes only.

[1] - Nakamura, Kazuo. “Aniracetam: Its Novel Therapeutic Potential in Cerebral Dysfunctional Disorders Based on Recent Pharmacological Discoveries.” CNS Drug Reviews, vol. 8, no. 1, July 2006, pp. 70–89., doi:10.1111/j.1527-3458.2002.tb00216.x.

[2] - Nakamura, Kazuo, et al. “Site-Specific Activation of Dopamine and Serotonin Transmission by Aniracetam in the Mesocorticolimbic Pathway of Rats.” Brain Research, vol. 897, no. 1-2, 2001, pp. 82–92., doi:10.1016/s0006-8993(01)02096-0.

[3] - Senin, Umberto, et al. “Aniracetam (Ro 13-5057) in the Treatment of Senile Dementia of Alzheimer Type (SDAT): Results of a Placebo Controlled Multicentre Clinical Study.” European Neuropsychopharmacology, vol. 1, no. 4, 1991, pp. 511–517., doi:10.1016/0924-977x(91)90004-e.

[4] - Lee, C. Rhoda, and Paul Benfield. “Aniracetam.” Drugs & Aging, vol. 4, no. 3, 1994, pp. 257–273., doi:10.2165/00002512-199404030-00007.

[5] - Koliaki, Chrysi C., et al. “Clinical Efficacy of Aniracetam, Either as Monotherapy or Combined with Cholinesterase Inhibitors, in Patients with Cognitive Impairment: A Comparative Open Study*.” CNS Neuroscience & Therapeutics, vol. 18, no. 4, 2011, pp. 302–312., doi:10.1111/j.1755-5949.2010.00244.x.