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L'affinité du modafinil pour le récepteur alpha-2 est plus élevée que pour le récepteur alpha-1. Certains ont émis l'hypothèse que bien que le modafinil n'améliore pas l'attention par rapport à d'autres stimulants, il peut produire un effet psychologique en réduisant l'inhibition dans le cerveau, augmentant ainsi l'excitation. Il peut agir en agissant plus ou moins directement sur les récepteurs de la dopamine et/ou en inhibant la pompe de recapture de la dopamine. On pense que le modafinil agit en améliorant l'éveil en inhibant la libération de certaines substances (dopamine, norépinéphrine et sérotonine) qui sont impliquées dans la « pulsion de sommeil », permettant à une personne de rester éveillée pendant de plus longues périodes. 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Des doses de 800 mg sont souvent utilisées pour traiter les symptômes modérés de la narcolepsie, où une somnolence excessive interfère avec les performances. Le 7e de novembre 2006, la Food and Drug Administration (FDA) des États-Unis a approuvé le modafinil comme traitement de la somnolence excessive associée à l'apnée obstructive du sommeil. Dans une revue médicale, les États-UnisLa Food and Drug Administration (FDA) note que le modafinil est "bien toléré" et "peut avoir moins, voire aucun, des effets indésirables observés avec les stimulants commercialisés pour le traitement du trouble d'hyperactivité avec déficit de l'attention (TDAH)", y compris "mauvais rêves, bouche sèche, somnolence, maux de tête, cauchemars, agitation, hypertension artérielle, convulsions et insomnie. 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