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Dopamine transporter (DAT)weakly inhibits reuptake

Orexin (hypothalamic wake system)increases signaling

Histamine (tuberomammillary)increases signaling

Prodrug hydrolysis to flmodafinil (CRL-40,940)Fladrafinil is a hydroxamic acid that is hydrolysed in vivo to the corresponding amide, flmodafinil, which carries the pharmacological activity

Dopamine transporter (DAT, SLC6A3)Dopamine reuptake inhibition, attributed to the active metabolite flmodafinil rather than to fladrafinil itself

Dopamine transporter (DAT)weak selective inhibitor

Norepinephrine transporterinhibits

Orexin / histamineraises

Dopamine transporter (DAT, SLC6A3)Inhibitor; blocks dopamine reuptake. The primary and only well-established direct molecular target.

Norepinephrine transporter (NET, SLC6A2)Negligible direct binding at attainable concentrations.

Serotonin transporter (SERT, SLC6A4)No meaningful interaction demonstrated.

Dopamine D2/D3 receptorsIndirect. Apparent occupancy changes because synaptic dopamine rises, not because modafinil binds the receptor.

Dopamine D1 receptorDownstream mediator of behavioural effect, not a binding site.

Orexin/hypocretin neurons (perifornical hypothalamus)Indirect circuit activation; not required for wake promotion.

Histaminergic tuberomammillary nucleus (TMN) neuronsIndirect circuit activation.

Mesencephalic dopamine neurons (VTA and substantia nigra pars compacta)Required downstream circuit for arousal.