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What is Nefiracetam?

Nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide; DM-9384) is a nootropic compound derived from piracetam. It was first synthesized by Nattermann in Germany and was subsequently developed by Daiichi Pharmaceutical Company in Japan. It has not been studied as extensively as its related compounds until more recently, and clinical trials are still underway.  It is approved for use in China and has been marketed under the trademarked names Translon and Motiva.

How does it work?

Nefiracetam exerts a number of different effects on several neurotransmitter systems in the brain. Like other racetam compounds, it has been shown to modulate acetylcholine neurotransmission by accelerating turnover and release. Unlike other racetam compounds, it can bind to GABA receptors. This interaction between nefiracetam and GABA receptors is believed to have favorable effects on memory consolidation. Nefiracetam may also augment ion flow into neurons through NMDA receptors that are near cholinergic (acetylcholine) receptors. NMDA receptors are subtype of ion channel that are essential for learning and memory. It also increases levels of enzymes needed to synthesize noradrenaline, dopamine, and serotonin in the hippocampus and frontal cortex.Strong anti-epileptic effects have also been observed in mice and rats, but the mechanism behind this remains unknown. Nefiracetam has also been used to increase blood flow to the brain of rats with occluded carotid arteries.

Nefiracetam Benefits

Studies in mice have demonstrated that nefiracetam significantly improves spatial memory; mice given the drug do better in mazes and on recognition tasks. Damage from insults such as ischemia (restricted blood supply/low oxygen) or anoxia (no oxygen) is reduced in animals that have been treated with nefiracetam. It has also been shown to improve learning in a rat model of Alzheimer’s disease, and clinical studies of nefiracetam for Alzheimer’s patients are ongoing. One study showed that nefiracetam prevented amnesia induced by propofol (the anesthetic of Michael Jackson fame). Interestingly, the compound may also be useful to treat chronic pain; it reduces thermal hyperalgesia in mice.

The effects in humans are still being investigated, but the clinical trials that have taken place suggest that nefiracetam may improve cognitive function and frontal lobe activity. It also has antidepressive effects; patients who had suffered strokes and had severe post-stroke depression had improved outlooks, decreased apathy, and higher energy after taking nefiracetam for at least 4 weeks (the study lasted 12 weeks).

Anecdotal benefits of nefiracetam in otherwise healthy people include improved recall, anxiolytic effects, better coordination, and improved attention/focus. However, controlled studies testing these theories have not been performed.

Nefiracetam Side Effects

As a rule the racetam family of compounds have excellent safety profiles. However, doses of 300 mg/kg per day have been shown to decrease testosterone levels and increase estradiol levels in male beagle dogs. There are also studies that report bladder toxicity with similar doses. It is important to keep in mind that this is a very large dose used to establish toxicity limits; the equivalent in an average size adult would be 21 g per day! It is unlikely that appropriate usage of nefiracetam would result in these side effects. Other, mild side effects reported include upset stomach.

Brain Games

Nefiracetam Dosage

Nefiracetam is fat-soluble, but its absorption can be slowed down by food. Therefore it is a good idea to take it first thing in the morning or on an empty stomach (although this may explain why some report nausea and stomach upset). It is available in capsules or as a powder and 600-1200 mg is the usual dosage, and a level ¼ teaspoon of powder is roughly 500-600 mg. Serum levels peak 2 hours after administration, and the half-life is 3-5 hours. As with other racetams, nefiracetam is commonly taken in conjunction with a choline supplement.

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