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

Biological Psychiatry 2010 November 16
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.

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