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Is a Step Backwards in S-Phase-Targeted Chemotherapy a Step Forward?

Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine Pittsburgh, PA 15260

SUMMARY

Orexin A (hypocretin-1) is regarded an essential mediator between energy homeostasis and the regulation of sleep/wake rhythmicity. Given that malfunctions of the orexin system are the hallmark in the pathophysiology of sleep-wake disorders, targeting central nervous orexin A pathways might be a valuable therapeutic option. Recent experiments comparing the cognitive effects of intranasal vs intravenous orexin A in sleep-deprived rhesus monkeys suggest that intranasally applied orexin A effectively reaches and modulates brain circuitries that control alertness. These exciting new findings are discussed in the context of previous research on the intranasal administration of neuropeptides in humans. The ramifications for the future clinical use of intranasally administered orexin A are considered.