By Colin, Kush, Eva, Michael and Gordon

Drugs that target orexin receptors

Very recently, there have been developments into drugs that target other receptors such as suvorexant which targets the orexin receptors. Like GABA, orexin peptides are known to play a role in sleep-wake cycles. The orexin peptides are produced by a cluster of neurons in the hypothalamus that have extensive projections to many brain regions, especially regions of the brain associated with arousal and wakefulness (Fig. 1). These areas include the LC, the TMN, the serotonergic neurons of the raphe nuclei, and dopaminergic neurons of the ventral tegmental area (VTA) (12). The orexin neurons also innervate the basal forebrain which plays a critical role in cortical activation and REM sleep (13). Orexin receptors in general are known to promote arousal. Drugs such as suvorexant work by binding orexin neuropeptides A and B, which inhibits their binding to orexin receptors 1 and 2 (OX1 and OX2) and inhibiting wakefulness (1412). 

Figure 1. Flowchart indicating regions of the brain that interact with orexin neuropeptides and some of the behavioral effects of orexin receptor signaling. Orexin receptors are associated with regions of the brain involved in arousal and wakefulness (12).

6 Comments

  1. Jinpeng Chen

    Similar to the section that discuss about GABA, I think this section also did a good job on explaining the mechanistic view of orexin receptors. I think an improvement that can made upon is diagram of how suvorexant bind to orexin receptors and induce the signal pathway.

  2. Robert McDermott

    Alot of your figures are titles figure 1. Maybe you could order them how they are used? I guess this is more preference however. Nice page.

    • Robert McDermott

      Since this page is not as in depth as previous on receptor functions, perhaps adding some current research focus on these receptor mechanisms and pathways that need to be uncovered or questions you may have would be good to supplement this.

  3. Monali H. Zhao

    This page gives a pretty concise explanation about orexin. I especially like the figure; it supplements the explanations well.

  4. Andrew W. D'Amico

    Nice page. I think the figure does a good job of showing effects clearly and demonstrates visually what you are trying to say in the text. One possible improvement could be going into more depth about the binding of Orexin, either using some type of media to display this or explaining it verbally.

  5. Matthew R. Shapiro

    I really like how short and to the point this page is. Even with being concise, it provides a great explanation of orexin receptors. The only thing I might change would be in the beginning of the paragraph, where orexin is compared to GABA as an analog. I think a slightly more specific comparison between GABA and Orexin is required here.

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