Selective targets for arousal-modifying drugs: implications for the treatment of sleep disorders

The level of arousal reflects the interaction between wakefulness-promoting and sleep-promoting nuclei located in the hypothalamus and brainstem. The nuclei and their connections constitute the sleeparousal network. Mapping out this network, together with the neurotransmitters involved, has created a unique opportunity for the design of drugs for sleep disorders-it has become possible to target specific sites within the network with predictable effects on the level of arousal. Recent examples of this approach are orexin receptor and 5HT(2A) serotonin receptor antagonists and melatonin receptor agonists for the treatment of insomnia, and H3 histamine receptor antagonists for the treatment of excessive daytime sleepiness.