Orexin Receptor Antibodies

The orexins (orexin-A and orexin-B, also known as hypocretin-1 and hypocretin-2) are neuropeptides derived from a single precursor expressed in the posterior lateral and medial hypothalamus. These peptides were discovered independently. The name orexin (after orexis, Greek for appetite) was derived from experiments showing increased food intake after intracerebral administration of the peptides in rodents. The name hypocretin reflects their hypothalamic expression and sequence similarity to the incretin peptide family. While their effect on appetite is still controversial, and may be the result of increased arousal, orexins have a prominent role in promoting wakefulness and stabilizing vigilance state as demonstrated by pharmacological or genetic modulation of the orexin receptor signalling. Mutations in the OX2 receptor are responsible for canine narcolepsy, and orexin neuron loss is associated with the human disorder. Targeted mutagenesis of the gene encoding the orexin ligands, or genetically induced postnatal destruction of orexin-producing neurons in rodents results in a salient narcoleptic phenotype. Small molecule orexin receptor antagonists have been shown to increase sleep across species, including man. Suvorexant was the first orexin receptor antagonist approved for the treatment of insomnia.