The mechanisms of action of modafinil are complex and not completely understood. Early data suggests it may operate on dopamine, serotonin, norepinephrine, histamine, orexin, glutamate, and GABA receptors, according to a number of sources. Below we have elaborated its effect on various neurotransmitters of brain –
Some data suggests that modafinil may enhance serotonin levels in a few parts of the brain.
When combined with antidepressants modafinil has been shown to have synergistic effects in a few experiments in cells and animals. Despite encouraging early investigations in animals and cells, a human study (double-blind randomized controlled trial) found no synergistic effects for the treatment of depression when modafinil and antidepressants were given together for major depressive disorder (MDD) with fatigue and sleepiness.
According to findings from a few early animal and cell investigations, modafinil may interact with the norepinephrine transporter (NET), resulting in a rise in norepinephrine levels throughout the brain. Norepinephrine aids in the mobilisation of the brain for action and can boost energy and alertness.
Some preliminary research suggests that modafinil works by partially blocking the dopamine transporter (DAT), which increases dopamine levels. Although modafinil has the same mechanism of action as cocaine, its effects on the dopamine transporter are said to be less and gentler, more equivalent to a soothing impact than cocaine’s “stimulant” effects.
Modafinil also partially activates the dopamine D2 receptor, which may increase alertness by increasing dopamine release across the brain, according to a few early animal studies.
Some researchers believe that modafinil’s actions on the dopamine receptor are to blame for some of the drug’s claimed motivation, confidence, and task pleasure effects.
Histamine and Orexin
According to reports from several early animal experiments, modafinil may also boost histamine release by acting on orexin-releasing neurons. Orexin is a neurotransmitter that is thought to contribute to overall arousal and alertness. Some experts believe that modafinil’s influence on orexin may contribute to the drug’s primary stimulatory effect.
Glutamate and GABA are two different types of amino acids.
Modafinil has been shown to increase the excitatory neurotransmitter glutamate release while lowering the inhibitory neurotransmitter GABA activity. However, several of these studies have revealed contradictory findings and region-specific effects, thus the actual mechanism is still unknown, and more study is needed.