Drugs to interfere with orexins (hypocretins).
Orexins (hypocretins) are bioactive peptides linking arousal, appetite and neuroendocrine-autonomic control. Dysfunction of the orexin system is associated with narcolepsy-cataplexy. Here, we review drugs interfering with orexins directly such as novel selective orexin receptor agonists and antagonists, as well as drugs interfering with orexins indirectly such as those used for the treatment of narcolepsy-cataplexy, and pharmacological targets within the complex network of endogenous neurohumoral signals integrated and relayed by the orexin system. These include amines, acetylcholine, purines, GABA and glutamate, as well as nutritional-metabolic, circadian-photic, immunological and neuroendocrine-peptidergic influences. Basic and clinical evaluation of drugs interfering with the orexin system will lead to a better understanding of the molecular prerequisites that control behavioral state, stress responses, energy homeo- stasis and survival, and yield therapeutic advances for the treatment of narcolepsy and other disorders of sleep, eating, mood and memory.
Selbach
Oliver
O
Department of Neurophysiology, Heinrich-Heine- University, Dusseldorf, Germany. selbach@uni-duesseldorf.de
Eriksson
Krister S
KS
Haas
Helmut L
HL
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002385:Cataplexy / Q000188:drug therapy / Q000473:pathology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009290:Narcolepsy / Q000188:drug therapy / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000502:physiology; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology
D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide