Which mechanism best describes modafinil’s action for narcolepsy?

• A. Orexin (hypocretin) agonist
• B. Dopamine antagonism
• C. GABA agonism
• D. Serotonin reuptake inhibition

Answer: (A)

Narcolepsy is driven by a deficiency in orexin (hypocretin) signaling, so therapies that boost this system help sustain daytime wakefulness. Modafinil works by activating the orexin/hypocretin system, promoting arousal and alertness. This aligns with the condition’s underlying problem and explains why modafinil improves daytime wakefulness. It can also subtly increase dopamine levels by weakly inhibiting the dopamine transporter, which supports alertness, but its defining action is enhancing orexin signaling rather than directly blocking or activating dopamine receptors. It is not a GABA agonist and not a serotonin reuptake inhibitor, so those mechanisms do not describe how modafinil promotes wakefulness.