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Armodafinil is a brain-enhancing drug that is quickly cutting into Adderall and Ritalin’s market share for treating inattentiveness, a lack of focus, mental fatigue and excessive sleepiness.
This eugeroic stimulant is capable of producing long lasting mental arousal and alertness without causing agitation, irritation or other unpleasant side effects so often inherent to central nervous system stimulants.
Armodafinil pills are seen as safe alternatives for individuals with ADHD and they are also seeing increasing demand from people who want to increase their productivity or academic success.
While research into how Armodafinil works is still ongoing, there have been some important observations made regarding its pharmacology.
In this article, we will explore Armodafinil’s Mechanism of Action to see what clues are offered for how this drug is able to produce its many benefits.
Energy
Cognition
Motivation- Wakefulness-boosting stimulant
- Enhances motivation and focus
- Shown to boost mental performance
Armodafinil History
Related Topics
- What is Armodafinil?
- What is Nuvigil?
- Armodafinil vs. Modafinil
- User Review
- Typical Nuvigil Experiences
- How it Works
- Nuvigil for ADHD
- Effects on Depression & Anxiety
- Dosage Recommendations
- How to Take
- Reported Side Effects
- Withdrawal & Tolerance
- Prescription Information
- Buying Nuvigil
- Generic Nuvigil Brands
- Is Armodafinil Legal?
- Is Nuvigil Safe?
- Comparison to Adderall
Earlier versions of Armodafinil, known as Adrafinil and Modafinil, were developed by the French pharmaceutical company, Lafon Laboratories.
Adrafinil is one of a series of benzhydryl sulfinyl compounds that was developed in 1974. During testing to determine how Adrafinil works in the body, Modafinil was discovered in 1976.
It was observed that Adrafinil is transported to the liver and metabolized into its component parts, the inactive modafinilic acid, and the active Modafinil. The compound Modafinil was found to be the primary active component of Adrafinil , and what causes its effects in the body.
The original drug, Adrafinil was first tested in animals and seen to have a stimulating effect, causing increased locomotor activity and hyperactivity at large dosages. The first human tests were done using Adrafinil to treat the sleep disorder narcolepsy. Adrafinil was approved as a treatment for narcolepsy in France in 1986.
Once researchers were able to synthesize the Modafinil drug directly, it was studied and used more than Adrafinil, as it is more potent and faster acting. Modafinil as well was tested and approved to treat narcolepsy in France in 1994 and in the United States in 1998.
Lafon ceased production of Adrafinil and focused on Modafinil (although Adrafinil is now once again produced by other manufacturers). Lafon was bought by Cephalon Inc in 2001, who continued making the most popular name brand version of Modafinil, Provigil.
The company was granted a patent on Modafinil and profited exclusively from the sale of the medication for a 10-year period. Then, as the time on the patent was running out, researchers went back to work and found a way to chemically alter Modafinil, by making it more pure.
This is done by using only one of the two mirror isomers that make up Modafinil. The practice of refining a drug to a single isomer is not uncommon and, sometimes, it is useful in ridding the drug of certain side effects. This new purer version of Modafinil is the drug Armodafinil.
The brand name versions of Provigil Modafinil and Nuvigil Armodafinil are still produced today by Cephalon, who is now a subsidiary of Teva Pharmaceutical Industries after they were acquired in 2011.
Armodafinil’s Mechanism of Action
Drugs possess two stereoisomers, or enantiomers–the R and S. These are compounds that are the same molecular structure, but are mirror images of each other (like right and left hands).
In some drugs, both of these enantiomers are not necessary for the therapeutic effects of the drug to occur. In fact, sometimes one isomer is the active one while the other is mostly inactive, or may even be the cause of some of the problems users experience when taking the drug.
Modafinil is a racemic compound, meaning that it is comprised of both R-Modafinil and S-Modafinil in equal proportions. In research it has been determined that the R-Modafinil isomer is the more metabolically stable and longer-acting enantiomer.
Armodafinil is simply the R-enantiomer of Modafinil alone, without the S-enantiomer – hence the name, Armodafinil, from R-Modafinil.
Like many psychostimulants, it is unknown exactly how Armodafinil produces the effects the user experiences, but many studies have been done on both Armodafinil and Modafinil which give us some indications as to what brain processes are being affected.
Adrafinil, Modafinil, and Armodafinil are all classified as eugeroics, or wakefulness promoting compounds. They have stimulant-like effects, but are not related to amphetamine or methylphenidate stimulants, and have different effects in the brain and body.
While the exact mechanism of Modafinil is still unknown, it has been seen to affect a variety of neurotransmitters, their receptors, and/or their transporters in the brain and central nervous system, including Dopamine, Serotonin, Norepinephrine, Epinephrine, Orexin (Hypocretin), and Histamine.
As it is essentially a purified version of Modafinil, it stands to reason that the effects of Armodafinil may be very similar to the effects of Modafinil on neurotransmitters in the brain, however more research is needed to validate this theory.
In research, Armodafinil had been observed to not be a direct or indirect Dopamine receptor agonist (it does not bind to Dopamine receptors). However, when studied in vitro, Armodafinil does inhibit the reuptake of Dopamine at the Dopamine transporter (DAT) site.
This action as a Dopamine transport and reuptake inhibitor causes an increase in extracellular Dopamine, which is to say there is more Dopamine circulating around your neurons.
- Increases energy, wakefulness and motivation
- Boosts mental performance and focus
- Supports memory and cognition
Researchers speculate that Armodafinil (sold under the name Nuvigil) appears to act on a specific subset of brain pathways which regulate sleep and wakefulness.
Modafinil has been seen to act on Orexin and Histamine, and it is thought this may be where most of its effects come from. Orexin is a neuropeptide that is strongly activated by Modafinil. The Orexin in turn stimulates the release of the neurotransmitter Histamine in the hypothalamus.
Both Orexin and Histamine are necessary for the regulation of wakefulness, arousal, and appetite. It is thought that Armodafinil may also have an effect on Orexin and Histamine like Modafinil does, although more research is needed in this area.
Some studies indicate Armodafinil may work in a similar manner as other sympathomimetics (including amphetamines) but Armodafinil’s mechanisms seem to be more specifically targeted to the brain’s sleep response system, rather than as a generalized central nervous system stimulant.
Other studies indicate Armodafinil’s mechanism of action involves other neurotransmitters, as well, though the exact method/s is unknown.
In one research study, when they blocked Armodafinil’s ability to effect these other neurotransmitters, the drug still was able to produce the wakefulness effect for which it was developed. Clearly, there is more work to be done before we gain a clear understanding about how Armodafinil and other eugeroic medications work.
Much funding and research is taking place in the field of neuroscience right now with new understandings and knowledge being gained consistently. Some of this research should help us to pinpoint how drugs like Armodafinil can produce the therapeutic benefits they do. Until that time, researchers remain unable to conclusively unlock the riddle of how, exactly, Armodafinil works.
On-Label and Off-Label Uses
In the United States, the FDA has classified Armodafinil as a Schedule IV prescription drug, just like its parent compound Modafinil. Armodafinil is similarly classified as a prescription medication in many other countries around the world.
In the US, Armodafinil has been officially approved as a treatment for narcolepsy and shift-work sleep disorder, and as an adjunct treatment for the excessive sleepiness of obstructive sleep apnea/hypopnea syndrome. In some places it is also used as a treatment for idiopathic hypersomnia, a sleep disorder similar to, but often less severe than, narcolepsy.
In some double-blind placebo-controlled clinical trials, Armodafinil has been seen to significantly improve wakefulness and decrease the excessive daytime sleepiness of narcolepsy compared to a placebo.
In one study, Armodafinil improved scores on the Epworth Sleepiness Scale and the Clinical Global Impression of Change scale, as well as significantly increased mean sleep latency as measured by the Maintenance of Wakefulness test.
Similar effects have been seen when Armodafinil has been tested for shift-work sleep disorder (SWSD) and obstructive sleep apnea/hypopnea syndrome (OSAHS).
In studies done on people with SWSD or OSAHS that is being treated with CPAP but still presents residual sleepiness, Armodafinil has been seen to improve wakefulness and reduce excessive sleepiness better than a placebo.
Armodafinil is also used off-label for a variety of uses. It has been used to relieve the fatigue associated with a number of diseases, including bipolar depression, multiple sclerosis, fibromyalgia, and Parkinson’s disease.
One of the most common off-label uses of Modafinil is to improve the symptoms of attention-deficit hyperactivity disorder (ADHD). There have been multiple studies done showing significant improvement on a number of tests of ADHD symptoms including the DSM-IV ADHD Behavior Checklist using Modafinil compared to placebo.
There have not been many studies done using Armodafinil for this purpose, and research needs to be done to determine if it could have even better results than Modafinil.
The most popular off-label use of Modafinil and Armodafinil is using these compounds as smart drugs or cognitive enhancers. Users report that Armodafinil improves concentration, focus, motivation, learning ability, and memory, much the same way Modafinil is said to.
Armodafinil Side Effects
Armodafinil is generally well tolerated when taken at dosages recommended by doctors for treating specific conditions. There are some mild side effects to be aware of though, including: headaches, nausea, dizziness, insomnia, anxiety, diarrhea, dry mouth, depression, and indigestion.
Some mild side effects can occur when you first begin taking any new medications, as they body adjusts to the drug. It is possible that you may experience side effects for the first two or so weeks that you take Armodafinil, but then these effects should subside.
If you are still experiencing side effects after a few weeks, then it is possible that the dosage is too much for your personal physiology and a lower dosage may be better. Lower your dosage for a few weeks and monitor if side effects subside (speak with your doctor first). If the side effects cease and the benefits you need are still present, then consider staying at the lower dosage.
If you are not getting the benefits you need, then slowly increase your dosage back to the higher level over a week or more, checking for side effects. If side effects start again then it is possible this drug is not a good fit for your physiology. Speak with your doctor about a different treatment for your needs.
One common side effect, insomnia, is not a true side effect typically, and more commonly is caused by poor timing of dosages. Armodafinil has a long half-life of between 13-15 hours. If you take a dosage too late in the day then it can still be active when you are trying to sleep. Try taking your dosage in the morning to avoid sleep disturbances.
Some rare, but serious skin rashes are possible when using Armodafinil, including Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). There is strong evidence showing that there is a genetic predisposition some people have the makes them susceptible to developing these skin conditions when they take drugs that are metabolized in the body a certain way, including Armodafinil.
Stop taking Armodafinil and speak with your doctor immediately if you have flu-like symptoms, a fever, and a red/purple spreading, blistering rash near the mouth, nose, eyes, and genitals.
Non-Prescription Alternatives
Many people want to try Modafinil or Armodafinil for nootropic purposes, however it can be nearly impossible to get a prescription without having a serious sleep disorder that is one of the approved on-label uses. Sometimes people will be able to get an off-label prescription written if they have ADHD, but this is still hard to do for most.
Some people will turn to the internet gray market to buy generic Modafinil and Armodafinil from international online pharmacies that do not require a prescription, however these places have inherent risks associated with them.
Your product could be seized by customs officials and not released to you if you do not have a prescription. Or if you do manage to receive your package, then there is no definite way to know that the product you received is in fact pure Armodafinil, as most of these vendors do not provide Certificates of Analysis or proof of good manufacturing practices.
Many people instead decide to use a non-prescription alternative to Armodafinil to experience nootropic effects. Some of the most popular alternatives are Adrafinil and one of the Racetams.
As described before, Adrafinil is the prodrug of Modafinil. The compound is broken down in the liver and then acts in a similar manner to straight Modafinil. Many people use it as an alternative when they cannot get a Modafinil or Armodafinil prescription.
Because it is processed in the liver, there is a possibility of elevated hepatotoxic liver enzyme levels if it is used on a regular basis. Therefore it is often recommended to only be used occasionally, as needed for a mental boost when working on a difficult work task, or studying for an exam.
The Racetams are a group of compounds all based on the parent compound Piracetam. First developed in the 1960s, Piracetam has been observed to have positive effects on the cholinergeric system, and is thought to increase the activity of Acetylcholine, leading to increased memory formation and retention, as well as enhanced general cognition.
Since the development of Piracetam, more potent derivatives have been developed, including Aniracetam, Oxiracetam, Pramiracetam, and Phenylpiracetam. The derivatives of Piracetam all have effects on Acetylcholine like their parent compound, but also vary from each other in terms of additional benefits and strength.
For example, when comparing the potency of Oxiracetam vs Piracetam, Oxiracetam is considered 3-5 times stronger than Piracetam, and has a greater effect on memory and learning ability. Phenylpiracetam on the other hand, it considered between 50-60 times as strong as Piracetam, and has been seen to have a strong effect on mental energy and alertness, which makes it an ideal substitute for Armodafinil for some people.
Summing It Up
Armodafinil is sold under the brand name Nuvigil. It is prescribed to treat narcolepsy, obstructive sleep apnea and shift work sleep disorder (SWSD). Other off-label, potential uses for this drug include ADHD, excessive daytime sleepiness, Parkinson’s disease, and mytonic muscular dystrophy.
Nootropic users benefit from increased focus, wakefulness and task orientation. The effects of Armodafinil are a crisp natural sense of wakefulness and vigilance, usually combined with an increased ability to focus on tasks and projects.
Common side effects include headache, nausea and irritability.
Armodafinil is contraindicated for those taking multiple other drugs, those with seizure disorder and pregnant or lactating women. Potential users should consult with their doctor before taking this drug.
The mechanisms of action of Armodafinil are not fully understood but research is ongoing and should offer some answers in the future.
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Article last updated on: April 12th, 2018 by Nootriment