The orexin receptor agonists are coming. After years of managing narcolepsy with stimulants, sodium oxybate, and wake-promoting agents, we soon will have medications that target the root cause of the disorder: the loss of orexin signaling. These new drugs—developed by Takeda, Alkermes, and Centessa—aren’t just incremental improvements. They represent a genuine shift in how we understand and treat hypersomnolence disorders. In this episode, we will:<ul><li>Define what orexin is and why losing it destabilizes wakefulness, REM boundaries, muscle tone, and cognition</li><li>Learn how orexin agonists work—not as stimulants, but as replacement therapy for a missing neurotransmitter</li><li>Find out why OX2R is the key receptor, and how selective agonists restore stable wakefulness, reduce cataplexy, and normalize attention</li><li>Review the available clinical data from the new wave of programs: oveporexton (Takeda), alixorexton (Alkermes), and ORX750 (Centessa)</li><li>See what makes these drugs different from modafinil, amphetamines, solriamfetol, and oxybate therapies</li><li>Learn why Phase 1, Phase 2, and Phase 3 trials matter—with quick insights on how these drugs reached such strong results</li><li>Consider safety and side effects, including what Hy’s Law means and why regulators watch liver signals so closely</li><li>Look ahead to what these medications may mean for NT1, NT2, IH, and other hypersomnolence disorders in the coming years</li><li>Speculate why this class represents one of the most exciting moments in modern sleep medicine</li></ul>Produced by: Maeve Winter More <ul> <li>Twitter: <a href='https://twitter.com/drchriswinter'>@drchriswinter</a> </li> <li>IG: <a href='https://www.instagram.com/drchriswinter/'>@drchriwinter</a> </li> <li>Threads: @drchriswinter</li> <li>Bluesky: @drchriswinter</li> <li> <a href='https://www.amazon.com/Sleep-Solution-Why-Your-Broken/dp/0399583602'>The Sleep Solution</a> and <a href='https://www.amazon.com/Rested-Child-Tired-Irritable-Disorder/dp/0593330080/ref=tmm_pap_swatch_0?_encoding=UTF8&qid=1665968940&sr=1-1'>The Rested Child</a> </li> </ul> Thanks for listening and sleep well!

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#178 - Orexin Agonists Are Here: This Is The New Stuff

Sleep Unplugged with Dr. Chris Winter

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