Orexin Receptor Antagonism: A New Principle in Neuroscience

Orexins are hypothalamic neuropeptides interacting with G-protein coupled receptors in the brain. They play a role in the regulation of sleep–wake cycles in mammals, as suggested by the deficits in orexinergic function that are associated with rodent, canine and human narcolepsy. Selective or dual orexin1-receptor and/or orexin2-receptor antagonists or agonists that cross the blood-brain-barrier (BBB) may be of therapeutic interest for disorders of disturbed arousal and alertness. This article summarizes recent research to identify and characterize orexin receptor antagonists and their therapeutic potential for normalizing sleep in insomnia patients