Modafinil is a medication that promotes wakefulness. It is marketed under the brand name Provigil and was approved by the U.S. Food and Drug Administration (FDA) to treat sleepiness in sleep disorders such as narcolepsy or sleep apnea.

Modafinil also potentially can reduce fatigue in Charcot-Marie-Tooth disease (CMT).

How modafinil works

CMT is the name given to a group of diseases that lead to the progressive degeneration of the peripheral nervous system, which is responsible for controlling muscle movement and carrying sensory information to the brain.

The loss of these peripheral nerves results in progressive muscle weakness and a loss of sensation in the hands, feet, arms, and legs. In addition to these symptoms, many patients also experience fatigue, especially during exercise, which can affect quality of life.

Modafinil is a stimulant medication, but the exact mechanism of action is not well understood. In laboratory experiments, modafinil has been shown to bind to the dopamine reuptake pump and inhibit it. Dopamine is a neurotransmitter, or cell-signaling molecule, that plays an integral role in movement and cognition as well as in the release of other neurotransmitters.

When nerve signals are sent in the brain from one nerve cell to another, the nerve message must be transmitted chemically at the point where two nerve cells meet. This junction is called a synapse. Once a chemical signal like dopamine has been released into the synapse and the message has been received by the connected nerve cell, the neurotransmitter is taken back into the nerve cells that released it (called reuptake). This prepares the synapse for the next message to be sent.

By blocking the pump that removes, or reuptakes, dopamine, modafinil ensures that dopamine stays present in the synapse for longer and has a stronger effect in the brain. This may have an impact on alertness.

Modafinil also acts on other types of nerve cells that rely on different chemical signal called glutamate to convey nerve messages. Modafinil activates these so-called glutaminergic nerve cells, which promote wakefulness. These are the same nerve cells that molecules like caffeine act upon. By increasing the signals sent by these neurons, it is thought that modafinil increases wakefulness.

Modafinil also inhibits the function of gamma-Aminobutyric acid, or GABA, an inhibitory neurotransmitter. GABA acts to end nerve signals and to relax nerve cells after a message has been sent. Modafinil reduces the effect of GABA, which means that the nerve cells are more active.

The combination of the effects of modafinil appears to improve wakefulness and alertness in conditions like narcolepsy, but may also be useful in neurological disorders like CMT.

Modafinil in CMT 

Although modafinil has not been approved specifically for the treatment of CMT, research has shown that it can reduce fatigue in this group of patients.

A study published in the American Journal of Hospice and Palliative Medicine reported the case of four patients with CMT type 1A who experienced significant fatigue. That fatigue was almost completely relieved by modafinil. Patients were prescribed 200 mg of modafinil to be taken in the morning, and fatigue was assessed by patient reporting. One patient reduced his dose by half because he felt jittery, but after one month of taking 100 mg of modafinil, he reported significant improvement in his fatigue symptoms. One patient was able to reduce her dose of modafinil to 100 mg after three months. Another patient needed a second dose of 200 mg of modafinil to see a reduction in fatigue.

Other information

Modafinil may cause side effects, including headaches, nausea, anxiety, and nervousness.


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