In vivo activity of modafinil on dopamine transporter measured with positron emission tomography and [¹⁸F]FE-PE2I

Int J Neuropsychopharmacol. 2014 May;17(5):697-703. doi: 10.1017/S1461145713001612. Epub 2014 Jan 22.


Modafinil, a wake-promoting drug used to treat narcolepsy, is a dopamine transporter inhibitor and is said to have very low abuse liability; this, however, is still up for debate. We conducted a dopamine transporter (DAT) occupancy study with modafinil (200 or 300 mg) in ten healthy volunteers using positron emission tomography (PET) with [¹⁸F]FE-PE2I, a new PET radioligand with high affinity and selectivity for the dopamine transporter, to characterize its relation to abuse liability. Mean striatal DAT occupancies were 51.4% at 200 mg and 56.9% at 300 mg. There was a significant correlation between occupancy and plasma concentration, indicating dose dependency of DAT inhibition by modafinil in the striatum, and especially in the nucleus accumbens. This study showed that DAT occupancy by modafinil was close to that of methylphenidate, indicating that modafinil may be near the same level as methylphenidate in relation to abuse liability in terms of dopaminergic transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / blood
  • Benzhydryl Compounds / pharmacology*
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / metabolism*
  • Brain Mapping
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Modafinil
  • Nortropanes
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Wakefulness-Promoting Agents / administration & dosage
  • Wakefulness-Promoting Agents / blood
  • Wakefulness-Promoting Agents / pharmacology*
  • Young Adult


  • (E)-N-(3-iodoprop-2-enyl)-2beta-carbofluoroethoxy-3beta-(4'-methyl-phenyl) nortropane
  • Benzhydryl Compounds
  • Dopamine Plasma Membrane Transport Proteins
  • Nortropanes
  • Radiopharmaceuticals
  • Wakefulness-Promoting Agents
  • Modafinil