Scientists have high hopes that a new drug could serve as a breakthrough in addressing tiredness. The Japanese drug Oveporexton, which mimics the role of orexins—neurotransmitters in the brain that govern wakefulness—has received approval for use in the US, reports BritPanorama.
While Oveporexton is primarily aimed at treating narcolepsy, researchers are optimistic it may also alleviate exhaustion and enhance concentration. This approach parallels the trajectory of Ozempic, originally developed to treat diabetes before it became widely recognized for aiding weight loss.
Dr. Michael Colwell, a postdoctoral researcher in the Department of Psychiatry at the University of Oxford, describes orexin as “perhaps one of the last major stones left unturned in brain chemistry.” He explained, “We’re starting to better understand what keeps the brain online and ticking, and orexin is emerging as a central player here, alongside histamine.” Recent methodological advances have enabled the identification of drugs that effectively target the orexin system.
Additional drugs mimicking orexin, often referred to as orexin agonists, are advancing toward market availability. For individuals with narcolepsy who cannot produce orexin, the absence leads to sleep paralysis; these individuals may find themselves fully awake yet suddenly collapse due to an unexpected, temporary paralysis.
While orexin agonists are a recent addition to the market, the first drug countering the action of orexin, suvorexant, was approved by the US Food and Drug Administration 12 years ago. There is growing interest in exploring new applications for such medications. Philip Cowen, a professor of psychopharmacology at the University of Oxford, asserts that evidence indicates orexin antagonists are comparable in effectiveness to commonly employed insomnia treatments. However, he notes they may offer longer-term benefits lacking in some alternatives.
“Also, it is claimed that these orexin drugs do not cause withdrawal symptoms and rebound insomnia [a temporary worsening of insomnia once medication is stopped] even after long-term use,” he stated. With Oveporexton, there is hope that the system regulating sleep and wakefulness can function optimally, addressing the underlying issues rather than merely alleviating symptoms.
Neurodivergence emergence
There is anticipation that new drugs targeting the orexin system may also provide treatment avenues for other conditions, including depression and ADHD. Experiments involving rats conducted by Japanese scientists revealed that stimulation of orexin neurons improved the animals’ motivation, as those neurons activated when faced with food rewards. Conversely, inhibiting orexin activity led to diminished motivation.
Researchers suggest that these findings may pave the way for treating individuals who struggle with goal-oriented behavior. Given the established link between sleep cycles and mood disorders, targeting sleep may represent a viable strategy for addressing low mood.
“One reason why people may be targeting orexin is that it sends these vast projections to these different areas [of brain activity] that have been shown to play a role in mood,” noted Dr. Dipesh Chaudhury, an associate professor of biology at New York University Abu Dhabi. However, he cautioned that it remains “too early to say” how significant targeting the orexin system will be in managing depression.
Dr. Chaudhury added, “In terms of depression research right now, and in terms of mood regulation with orexin, the potential is there – it’s a new avenue. But … the evidence for it to be one magic drug to cure mood disorders is not that clear to me.” He suggested that ketamine, known for treating treatment-resistant depression and acting more rapidly than traditional antidepressants, may hold greater importance.
While the potential for using orexins to treat sleep disorders appears promising, its effectiveness for addressing other psychological conditions may take years to be fully understood.
