In one trial of one of the main classes of prescription sleeping pills, half of the participants slept through a strong fire alarm like someone who was vacuuming near their bed. But a new alternative preserves the ability to wake up in response to signs of danger, according to new research.
Published this week in Frontiers in Behavioral Neuroscience the study showed that the mice gave the hypnotic experimental drug DORA -22 wake up quickly when threatened by drug-free sleepers – and then asleep as fast as those who have assumed standard sleeping pills once the threat disappeared.
Common sleeping pills absorb the intruder alarm of your sleeping brain
Even during sleep, the brain continually processes sensory information, waking up if it detects a threat. But the best known class of sleeping pills, known as benzodiazepines, makes us less likely to arouse sensory reactions.
"Benzodiazepines stimulate the widespread GABA-A brain receptor, which makes us sleepy but also suppress the brain's target areas ̵
In the past decade, researchers have developed a new class of hypnotic drugs called dual orexin receptor antagonists (DORA). The DORAs focus more selectively on the sleep / wake pathways of the brain, which gives them advantages in terms of safety compared to benzodiazepines. These include a reduced "hangover effect", with DORA less likely to affect driving ability the day after use.
Kuwaki and colleagues have hypothesized that the selectivity of DORAs could make them a safer alternative even during sleep – allowing brain sensations gatekeepers to remain alert to threats.
DORA-22 allows mice to wake up to a threat, but still helps them to sleep
The group has tested their theory in mice.
Mice were dosed and tested after dark, when they are normally more active. One group was given DORA-22, another a benzodiazepine called triazolam – and a third group was given placebo as a control.
"DORA-22 and triazolam had similar sleep-promoting effects, prolonging the duration of deep sleep by 30-40% compared to placebo," reports Kuwaki.
One to four hours after administration, the mice that slept soundly received a threatening urge: the smell of a fox, a sharp noise like a dog whistle, or the trembling of their cage. The trembling frequency was designed to match that of an earthquake – a serious threat in Japan from Kuwaki and many other parts of the word.
"As expected, the excitement in response to these menacing stimuli was significantly delayed in triazolam treatment, but not in the DORA-22 treatment, compared to placebo.
Even more promising, the & # 39; DORA-22 sleep promotion effect remained after the rude awakening.
"Although the mice treated with DORA-22 were quickly awakened by a threat, they subsequently quickly fell asleep as with the triazolam and significantly faster than with placebo. "
To help show that the delay in awakening a threat during treatment with triazolam was specifically due to the inhibition of sensory gating in the brain, the researchers also tested the dormant mice with a non-sensory stimulus.  "The three groups woke up equally quickly when we suddenly reduced the amount of oxygen in their cage. This suggests that the delay in stimulating the menacing stimuli caused by triazolam was not caused by a general inhibition of waking systems in the brain. "
Human studies are needed to confirm the safety and effectiveness of DORA
" Although it remains to be seen whether the Dora have the same properties when used in the Man, our study provides important and promising information on the safety of these hypnotics. "
Since 2014, another DORA called surovexant has obtained regulatory approval in Japan, the United States and Australia. So far, the 39, high cost and limited clinical trials of surovexant have limited its use, among the concerns that high enough doses to significantly improve sleep lead to drowsiness the following day.New DORA currently in development could overcome this effect after-effects are released more quickly from the body compared to suvorexant, so that their effects are less likely to last longer than bedtime.
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