Scientists hope a new drug could be a silver bullet when it comes to tackling tiredness.
The Japanese drug Oveporexton, which mimics the role of orexins, the neurotransmitters in the brain that regulate staying awake and being alert, has been approved for use in the US.
While the drug is designed specifically to treat narcolepsy, researchers hope it can also be used to tackle exhaustion and improve concentration – not unlike how Ozempic was first used to treat diabetes before it became famous for helping with 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”.
“We’re starting to better understand what keeps the brain online and ticking, and orexin is emerging as a central player here, alongside histamine,” he said.
“This has, in turn, been enabled by recent methodological advances uncovering drugs that effectively target the orexin system.”
Other drugs that also mimic orexin, known as orexin agonists, are moving closer to market.
Some narcoleptics are unable to produce orexin, which prevents the paralysis that takes place during sleep from happening during wakefulness. As a result, wide-awake narcoleptics may fall to the floor after experiencing a sudden, temporary paralysis.
While orexin agonists are new to the market, the first drug that works against the action of orexin, suvorexant, was approved by the US Food and Drug Administration 12 years ago and there is interest in finding new ways to use such medicines.
Philip Cowen, professor of psychopharmacology at the University of Oxford, says evidence suggests orexin antagonists are about as effective as commonly used insomnia medication.
But he indicated they may have a long-term efficacy that some other drugs for the same conditions lack.
“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 said.
With oveporexton, the hope is that the system controlling sleep and wakefulness will function properly. Unlike some other narcolepsy drugs, it treats the underlying problem rather than the symptoms.
Neurodivergence emergence
There are hopes the emergence of drugs targeting the orexin system may also treat other conditions, such as depression or ADHD.
Experiments on rats by scientists in Japan indicated their importance for motivation, because animals whose orexin neurones had been stimulated made greater effort to secure food. Also, suppressing orexin activity decreased motivation.
Orexin activity in the animals’ brains was also shown to surge when they waited for a food reward.
The researchers suggested their findings could open up ways to treat people who struggle with goal-oriented behaviour.
Given that the sleep cycle is often linked to depression, targeting it is one way of dealing with 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,” said Dr Dipesh Chaudhury, an associate professor of biology at New York University Abu Dhabi.
However, Dr Chaudhury said it was “too early to say” how important targeting the orexin system will be in dealing with depression.
“In terms of depression research right now, and in terms of mood regulation with orexin, the potential is there – it’s a new avenue,” he said. “But … the evidence for it to be one magic drug to cure mood disorders is not that clear to me.”
Ketamine, which is used for treatment-resistant depression and acts faster than many traditional antidepressants, may be more important, suggested Dr Chaudhury.
While there appears to be much potential for using orexins to treat sleep disorders, whether they will also be important for dealing with other psychological conditions could take years to be established.
