Serotoninergic reuptake mechanisms in the control of cataplexy

Zimelidine, a selective inhibitor of serotonin (5-HT) reuptake in the CNS, was administered to narcoleptic patients. This medication has a potent anticataplectic action without improving daytime somnolence. These results suggest that 5-HT neuronal systems are involved in the physiopathology of cataplexy. Zimelidine, however, has no anticholinergic effect, so it is unlikely that cholinergic mechanisms thought to be important in animal cataplexy would play a major role in human cataplexy. In addition, zimelidine had no effect on nocturnal sleep patterns of these patients which is surprising considering the importance of 5-HT neuronal systems in sleep physiology. A 5-HT hypothesis of cataplexy is formulated, and the mechanisms of action of other anticataplectic agents are discussed.