The drug can preserve the ability to wake up in the event of loud noises and reduces the so-called “hangover effect” caused by other sleep aids.

When we sleep, our brain still processes information, but this is not detrimental to sleep thanks to our thalamus. The thalamus is a small structure within the brain in charge of filtering sensory information — essentially, it blocks what it finds unnecessary or redundant.

Many sleep-aid sedatives work by enhancing the effects of GABA-A, a chemical with inhibitory qualities, thus slowing brain activity and facilitating sleep — but these central nervous system (CNS) depressants also augment the amount of stimulus necessary to wake someone up. In other words, it makes it more difficult for people to wake up in the case of an alarm — it has been reported that people under this drug’s effects were unable to wake up to the sound of a fire alarm.

Earlier this month, researchers from Kagoshima University in Japan revealed a new drug that does not impair the ability to wake in response to aversive incentives, when compared to CNS depressants or to consuming no hypnotics.

“The ability to awaken from sleep in response to important stimuli is a critical feature of normal sleep, as is maintaining sleep continuity in the presence of irrelevant background noise,” they write.

The drug, called Dora-22, works by blocking orexin receptors. Orexins, play an important role in regulating the states of arousal and sleep. The blockade caused by DORAs limits the chances of awakening, thereby encouraging sleep. However, previous studies have shown that the drug DORA-22 also allows subjects to wake in response to positive, conditioned stimuli — but it was yet to be proved if results would be similar in response to negative, innate stimuli.

Researchers experimented with different types of stimuli (auditory, vestibular, olfactory and hypoxic) on mice. They tested auditory stimulus using an intermittent ultrasonic sound of 100 dB, the equivalent of an industrial fire alarm. The vestibular stimulus was tested by shaking the animal’s cage at 180 rpm, for 30 seconds. For the olfactory stimulus, cotton containing
the odor of a fox was placed 1 cm away from the mouse.

They found very similar results for auditory, vestibular and olfactory stimulation. Essentially, DORA-22 proved to be as effective at promoting sleep as common drugs such as triazolam but allowed the mice to wake up much easier when subjected to different stimuli. There was also no increased delay until the mice reached peak alertness — so there was no hangover effect.

Further research is still needed to evaluate how the drug would perform on humans, but so far, it seems like a promising option towards treating insomnia, with minimal side effects.

Journal Reference: Iwakawa, S., Kanmura, Y., & Kuwaki, T. (2018). “Orexin receptor blockade-induced sleep  reserves the ability to wake in the presence of threat in mice.” Frontiers in Behavioral Neuroscience, 12, 327.