Modafinil is structurally unrelated to amphetamine and has a more limited profile of central neurotransmitter effects. It does not bind to monoamine or neuropeptide receptors or transporters, nerve membrane ion channels, or activate second messenger systems.
Increased Energy
Like caffeine, Modafinil is a stimulant that blocks adenosine receptors. However, unlike caffeine, which is purely a stimulant that only staves off sleep, Modafinil increases energy levels and concentration.
Modafinil 200 Australia has been shown to improve performance on tasks requiring cognitive control, such as working memory and delayed matching, in a dose- and delay-dependent manner. It also enhances recognition memory and sustained attention in healthy adults without sleep deprivation.
Interestingly, a study of scalp somatosensory evoked potentials found that a single modafinil 100 mg dose increased the short-latency component of high-frequency oscillations, with a widespread scalp distribution and uniform polarity, and dipole modeling suggesting a subcortical source likely located in the brainstem. However, the authors posited that these results may reflect modulation of other neurotransmitters in addition to DA.
Increased Focus
Modafinil has been shown to improve performance on complex tasks such as the Wisconsin Card Sort Test, a task that requires attention and executive function. One study of healthy adults with 85 h of sleep deprivation found that single-dose modafinil 400 mg reduced errors on the WCST, whereas no effect was seen in a placebo group. Similarly, Modafinil and Modalert 200 improved performance on the TOL spatial planning task, a task that requires attention and impulse control.
The ability of modafinil to reduce error rates without reducing accuracy has led scientists to suspect that it enhances neural efficiency. However, the site of action mediating this effect is still unclear. Interestingly, the CYP2C9 inhibitor prazosin abolishes modafinil’s effects on DA neurotransmitters and enhances extracellular gamma-aminobutyric acid in neocortical areas.
Increased Motivation
Although it is not as potent as amphetamine, modafinil has a very different profile of neurochemical and behavioral effects on central DA systems. It blocks DAT but does not seem to have a significant affinity for other monoamine transporters, neuropeptide receptors, or nerve membrane ion channels and appears to exert its stimulant effects through the inhibition of catecholamine degradation.
Modafinil increases extracellular levels of noradrenaline and serotonin in the medial prefrontal cortex (Ferraro et al, 2000). It also enhances the increase of extracellular serotonin induced by the antidepressants fluoxetine and imipramine: a dual-probe microdialysis study in awake rats.
Moreover, in a placebo-controlled fMRI study of narcolepsy patients, modafinil significantly improved CPT-IP, Letter-Number Span, and Decision-Making but not Working Memory or Flexibility of Thought. However, it did not improve CPT-IP or Letter-Number Span after the administration of dexamphetamine/methylphenidate.
Increased Concentration
Modafinil improves cognition by increasing acetylcholine and histamine levels in the prefrontal cortex, suggesting that it enhances a neurotransmitter system involved with cognitive control. In one study, a single dose of modafinil reduced errors on the Wisconsin Card Sorting Task (WCST) in sleep-deprived emergency physicians, who were blinded as to whether they had received a placebo or modafinil.
Another study found that a single dose of Modafinil and Modafresh improved performance on a task involving the use of serial visual stimuli, indicating that it improves memory by increasing the capacity to store information in long-term memory. This is consistent with the results of several other studies, showing that modafinil can increase the speed and accuracy at which individuals process information. Modafinil has also been shown to increase the extracellular concentration of dopamine in the striatum, including the nucleus accumbens, in a microdialysis study.
Increased Memory
Although modafinil may not improve performance on simple learning or memory tasks, it does appear to enhance cognitive flexibility and fluid intelligence. For example, in a study that asked participants to play chess while on the medication, modafinil resulted in fewer mistakes, but also led to increased time taken per move, which is associated with improved working memory.
In another study, healthy adults undergoing simulated night shifts found that a 4-day regimen of modafinil reduced errors on the Wisconsin Card Sorting Task and interference task compared to placebo, and enhanced performance on a version of the Hayling Sentence Completion Test that requires cognitive control. This effect was correlated with activation of the dorsolateral prefrontal cortex and anterior cingulate cortex as measured by fMRI.
Another clinical study found that narcolepsy patients taking a dose of 100-400 mg/day for three weeks had lower rates of anxiety than those on placebo and that their self-reported energy and motivation were higher on modafinil.
