Modafinil is one of the first manufactured nootropics and is currently the most popular medicine in the world. It is in the widespread use mostly as a smart drug that enhances learning, creativity, and memory of an individual. The FDA has approved the use of this drug for the treatment of narcolepsy, shift-work disorders, and obstructive sleep apnea, because people with these disorders have problems with excessive sleepiness, and Modafinil promotes alertness and is very useful in such patients.
Is Modafinil the best available nootropic on the market? In addition to Modafinil, there are many other nootropics of which Adrafinil, Fluorenol and Pitolisant are the most popular ones.
1. Modafinil vs. Adrafinil: Similarities and Differences
Both Adrafinil and Modafinil are drugs that belong to the group of nootropics and therefore have very similar pharmacological effects. Adrafinil is considered to be a mild stimulator of the central nervous system and is primarily used to alleviate excessive sleepiness and inattention in the elderly. It is not used in the treatment of narcolepsy while Modafinil is the first-line treatment for this disorder.
Adrafinil was not approved by the FDA, while Modafinil was approved long ago, in 1994. Adrafinil was approved for a short time in France during 2011, but its marketing authorization was withdrawn for unknown reasons.
Both drugs very rarely cause nervousness, anxiety and depression, which are the main feature of other psychostimulants, such as Adderall (Amphetamine).
From chemical and pharmacological point of view, these drugs are very similar, because Adrafinil is a prodrug of Modafinil. This means that when you take Adrafinil, it is converted into Modafinil in your body with the help of liver enzymes, after which it exhibits a similar effect to Modafinil.
However, because Adrafinil starts working after it passes through the liver; its effect starts much later than is the case with Modafinil. The effects of Adrafinil usually occur 1-2 hours later than with its opponent.
For the same reason, the recommended daily dose of Adrafinil is significantly higher (300-1200mg) than Modafinil (100mg).
Modafinil vs. Adrafinil: Side Effects
Modafinil has a significantly better safety profile than Adrafinil and does not have to pass through the liver in order to work.
One of the reasons why Adrafinil causes side effects more often than Modafinil is that its recommended daily dose is 3-10 times higher than for Modafinil. Clinical studies have shown that Adrafinil more often causes anxiety, abdominal pain, nausea, skin irritation, insomnia, nightmares, loss of appetite, restlessness, and high blood pressure.
Adrafinil can also cause severe hepatotoxicity, unlike Modafinil, which very rarely causes only a mild increase in liver enzymes.
2. Modafinil vs. Fluorenol: Similarities and Differences
Fluorenol is a medicine that has been reported as one of five active metabolites of Modafinil. That means that when you take Modafinil, it is converted in the body into its active metabolites that afterwards exhibit their effects. One of these active metabolites is Fluorenol.
Fluorenol exhibits a 40% more potent wake-promoting effect compared to Modafinil.
However, Fluorenol has a weaker effect (by as much as 60%) when it comes to dopamine reuptake, which is actually a good news, and because of that it has a lower potential for developing addiction compared to Modafinil.
Another advantage of Fluorenol is that it has a significantly lower affinity for the cytochrome P450 enzymes of the liver involved in the metabolism of numerous drugs. Therefore, Fluorenol has lower potential for interactions than Modafinil.
However, Fluorenol is a relatively newer drug and there are still not enough clinical studies on the safety and efficacy of this drug. Given that there are still no clinical studies in humans, the dose of this new drug has not been established yet.
The effects of Fluorenol last significantly shorter (only 4 hours) than with Modafinil (its effects last for about 15 hours).
Modafinil vs. Fluorenol: Side Effects
For now, only one side effect of Fluorenol has been reported – sleep paralysis. There are some data showing that this drug can cause brain damage, liver damage, cancer, and a significant impairment of the immune system.
On the other hand, Modafinil has been used for more than 20 years and its side effects are well known. So far, no deaths have been reported due to the use of this nootropic.
Although Fluorenol has more potent effects on cognitive functions than Modafinil and exhibits lower potential for dependence, further and more detailed studies are needed to define its safety profile.
3. Modafinil vs. Pitolisant: Similarities and Differences
Pitolisant is a nootropic that was recently approved by the European Medical Agency (EMA) for the treatment of narcolepsy with or without cataplexy. Unlike Modafinil, Pitolisant acts as an antagonist or inverse agonist of histamine H3 receptor, and enhances the effects of histaminergic neurons in the brain, while on the other hand, it exhibits significantly weaker effects on dopamine receptors.
Pitolisant as well as Modafinil is metabolized mostly by the cytochrome P450 enzymes of the liver, which is why both drugs have similar potential for interactions.
The effects of Pitolisant last somewhat shorter (around 10-12 hours) than with Modafinil.
The recommended dose of Pitolisant is 18-36mg a day, which is much less than recommended dosage for Modafinil.
Since it acts on histamine receptors, Pitolisant can cause drowsiness, which is why patients taking this medicine should avoid driving or operating machinery.
Modafinil vs. Pitolisant: Side Effects
The most common side effects reported with Pitolisant use include: insomnia (occurring in 8.4% of patients), headache (occurring in 7.7% of patients), nausea (occurring in 4.8% of patients), vertigo (occurring in 1.4% of patients), irritability (occurring in 1.8% of patients), fatigue (occurring in 1.1% of patients), and weight gain (occurring in 1% of patients). Modafinil can also cause all of these side effects in similar frequency as Pitolisant.
Pitolisant can also cause the following adverse reactions: decreased libido, panic attacks, restless leg syndrome, enterocolitis, gastroesophageal reflux, pain in extremities, and prolongation of QT interval, which manifests as irregular heartbeat.
Therefore, it is considered that Modafinil has a slightly better safety profile than Pitolisant.
Even Modafinil was discovered back in 1994, we haven’t seen a better nootropic yet, and Modafinil remains the best smart drug available on the market.