Cataplexy, an abnormal manifestation of REM sleep atonia, is currently treated with
antidepressants. These medications also reduce physiological REM sleep and induce nocturnal sleep disturbances. Because a recent work on canine
narcolepsy suggests that the mechanisms for triggering
cataplexy are different from those for REM sleep, we hypothesized that compounds which act specifically on
cataplexy, but not on REM sleep, could be developed. Canine studies also suggest that the
dopamine D2/D3 receptor mechanism is specifically involved in the regulation of
cataplexy, but little evidence suggests that this mechanism is important for REM sleep regulation. We therefore assessed the effects of
sulpiride, a commonly used D2/D3 antagonist, on
cataplexy and sleep in narcoleptic canines to explore the possible clinical application of D2/D3 antagonists for the treatment of human
narcolepsy. Both acute and chronic
oral administration of
sulpiride (300 mg/dog, 600 mg/dog) significantly reduced
cataplexy without noticeable side effects. Interestingly, the anticataplectic dose of
sulpiride did not significantly reduce the amount of REM sleep.
Sulpiride (and other D2/D3 antagonists) may therefore be an attractive new therapeutic indication in human
narcolepsy.