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Orexin (/ ɒ ˈ r ɛ k s ɪ n /), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. [5] It exists in the forms of orexin-A and orexin-B.The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or cataplexy), is caused by a lack of orexin in the brain due to destruction of the cells ...
Once made, the orexin peptides can bind to the orexin receptor; which is a G protein-coupled receptor. This receptor senses molecules outside the cell and activates inside signal transduction pathways to elicit cellular responses. Research shows that an absence of orexin-A appears to cause narcolepsy. Deficit amounts of orexin-A will make ...
The endocannabinoid system and the orexin system mediate many of the same cognitive and physical effects, and a significant overlap in their function and localization has been noted in a 2013 medical review; [4] the CB1–OX1 receptor heterodimer produces a 100-fold amplification of the potency of the orexin receptor 1-mediated ERK pathway ...
Lemborexant, an orexin receptor antagonist, was approved for use in the United States in 2019. Most ligands acting on the orexin system so far are polypeptides modified from the endogenous agonists orexin-A and orexin-B, however there are some subtype-selective non-peptide antagonists available for research purposes.
The orexin 1 receptor (OX 1), is a G-protein coupled receptor that is heavily expressed in projections from the lateral hypothalamus and is involved in the regulation of feeding behaviour. OX 1 selectively binds the orexin-A neuropeptide. It shares 64% identity with OX 2. [5]
Orexin: lateral hypothalamus; Excitatory effect on dopaminergic neurons via signaling through orexin receptors (OX1 and OX2) Increases both tonic and phasic firing of dopaminergic neurons in the VTA May interact with endocannabinoids via CB1–OX1 receptor heterodimers to regulate neuronal firing [44] [45] [46]
An orexin receptor antagonist, or orexin antagonist, is a drug that inhibits the effect of orexin by acting as a receptor antagonist of one (selective orexin receptor antagonist or SORA) or both (dual orexin receptor antagonis or DORA) of the orexin receptors, OX 1 and OX 2. [1] Medical applications include treatment of sleep disorders such as ...
Lemborexant is used in the treatment of insomnia in adults. [3]A major systematic review and network meta-analysis of medications for the treatment of insomnia published in 2022 found that lemborexant had an effect size (standardized mean difference (SMD)) against placebo for treatment of insomnia at 4 weeks of 0.36 (95% CI Tooltip confidence interval 0.08 to 0.63) and at 3 months of 0.41 (95% ...