A positron emission tomography study examining the dopaminergic activity of armodafinil in adults using [11C]altropane and [11C] raclopride

Thomas J. Spencer, Bertha K. Madras, Ali A. Bonab, Darin D. Dougherty, Allison Clarke, Tara Mirto, Jessica Martin, Alan J. Fischman

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background Armodafinil, prescribed principally to treat narcolepsy, is undergoing assessment of therapeutic potential for other neuropsychiatric disorders and medical conditions. The neurochemical substrates and mechanisms of armodafinil are unresolved. We investigated the hypothesis that armodafinil enhances wakefulness by modulating the activities of the dopamine transporter (DAT). With positron emission tomography imaging, we determined DAT occupancy and changes in extracellular dopamine by armodafinil in vivo. Methods Twelve subjects were enrolled. Plasma armodafinil levels were obtained. In vivo armodafinil occupancy of the DAT in striatum was detected by [ 11C]altropane and changes in extracellular dopamine were detected by indirect displacement of [11C]raclopride in human subjects at different times after drug administration. Results Armodafinil (100 mg by mouth [PO]) occupied striatal DAT (34.0 ± 9.0% at 1 hour, 40.4 ± 9.5% at 2.5 hours, n = 6) and 250 mg occupied striatal DAT (60.5 ± 7.4% at 1 hour, 65.2 ± 6.1% at 2.5 hours, n = 6). In addition, armodafinil was associated with changes in extracellular dopamine (17.8 ± 30.1% [100 mg PO] and 7.0 ± 8.6% [250 mg PO] at 2.5 hours, n = 6). Conclusions Occupancy of the DAT and changes in extracellular dopamine in vivo further implicates the actions of armodafinil on DAT as a potential candidate for its therapeutic improvement of wakefulness and other conditions.

Original languageEnglish (US)
Pages (from-to)964-970
Number of pages7
JournalBiological psychiatry
Volume68
Issue number10
DOIs
StatePublished - Nov 15 2010

Keywords

  • ADHD
  • neurochemical imaging
  • PET imaging
  • pharmacokinetics
  • stimulants
  • substance abuse

ASJC Scopus subject areas

  • Biological Psychiatry

Fingerprint Dive into the research topics of 'A positron emission tomography study examining the dopaminergic activity of armodafinil in adults using [<sup>11</sup>C]altropane and [<sup>11</sup>C] raclopride'. Together they form a unique fingerprint.

Cite this