Modafinil affects the activation of orexin-containing neurons. Neurons of the lateral hypothalamus exclusively produce orexin-A and orexin-B, neuropeptides made of 33 and 28 amino acids. These orexins act at axon terminals, increasing the release of the inhibitory transmitter GABA and the excitatory transmitter glutamate. This fact does not necessarily determine the mechanism of action for Modafinil, but confirms its action on the hypothalamus.
Modafinil also does not work unless the patient has a good alpha-one-adrenergic system, but does not appear to be a direct or indirect alpha-adregenergic agonist. The level of c-fos expression rises in patients on Modafinil, in certain areas of the brain. (Agonists are substances that bind to and cause a functional effect identical in quality and quantity to the endogenous ligand, in this case alpha-adregens.)
Unlike amphetamines and Ritalin, Modafinil does not act as a direct or indirect dopamine receptor agonist nor does it bind to possibly relevant receptors including those for norepinephrine, serotonin, gamma-aminobutyric acid (GABA), and dopamine uptake.
French scientists have recently determined that modafinil can help memory and other forms of mental performance in sleep-deprived mice. This meshes with reports of many humans who take modafinil and find the same thing.