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Original Article |
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Neuropsychopharmacology (2000) 23 528-538.10.1038/sj.npp.1395548
Sulpiride, a D2/D3 Blocker, Reduces Cataplexy but not REM Sleep in Canine Narcolepsy
Mutsumi Okura1,2 MD, Joyce Riehl1 AB, Emmanuel Mignot1 MD, Ph.D and Seiji Nishino1 MD, Ph.D |
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1Center for Narcolepsy, Stanford Sleep Center, Stanford University School of Medicine, Palo Alto, CA USA
2Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe, Japan
Correspondence: Dr Seiji Nishino, Center for Narcolepsy, Department of Psychiatry & Behavioral Sciences, 1201 Welch Road, MSLS Building, Rm. P113, Palo Alto, CA 94304-5485. Tel.: 650-723-3724; Fax: 650-498-7761; nishino@leland.stanford.edu
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ABSTRACT
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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.
Keywords: Narcolepsy; Cataplexy; Sulpiride; Dopaminergic System; REM sleep |
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