2013/01/01 by Jonathan P. Wisor · 1 citation
Neuroscience · Psychology · Medicine · #Sleep and Wakefulness Research #Sleep and related disorders #EEG and Brain-Computer Interfaces #Modafinil #Catecholaminergic #Neuroscience #Sleep (system call) #Psychology #Catecholaminergic cell groups #Medicine #Psychiatry #Cognitive science #Dopamine #Computer science
paper · pdf · doi:10.3389/fneur.2013.00139
openalex publication_date 2013/01/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
Modafinil, in its two clinical formulations (Provigil(®) and Nuvigil(®)), is a widely prescribed wake-promoting therapeutic agent. It binds competitively to the cell-membrane dopamine (DA) transporter and is dependent on catecholaminergic (dopaminergic and adrenergic) signaling for its wake-promoting effects. The clinical spectrum of effects for modafinil is distinct from the effects seen with other catecholaminergic agents. Relative to other commonly used agents that act through catecholaminergic mechanisms, modafinil has a relatively low abuse potential, produces wakefulness with an attenuated compensatory sleep recovery thereafter, and does not ameliorate cataplexy in narcolepsy. These clinically relevant phenomenological differences between modafinil and agents such as amphetamines and cocaine do not eliminate catecholaminergic effects as a possible mediator of its wake-promoting action; they merely reflect its unique pharmacological profile. Modafinil is an exceptionally weak, but apparently very selective, DA transporter inhibitor. The pharmacodynamic response to modafinil, as measured by DA levels in brain microdialyzate, is protracted relative to other agents that act via catecholaminergic mechanisms. The conformational constraints on the interaction of modafinil with the DA transporter - and probably, as a consequence, its effects on trace amine receptor signaling in the catecholaminergic cell - are unique among catecholaminergic agents. These unique pharmacological properties of modafinil should be considered both in seeking to thoroughly understand its putatively elusive mechanism of action and in the design of novel therapeutic agents.