Source:http://www.frontiersin.org/ Reviewed by Alina Shrourou, B.Sc. (Editor)Jan 11 2019In a trial of one of the main class of prescription sleeping pills, half the participants slept through a fire alarm as loud as someone vacuuming next to their bed. But a newer alternative preserves the ability to wake in response to danger signals, according to a new research.Published this week in Frontiers in Behavioral Neuroscience, the study showed that mice given the experimental hypnotic drug DORA-22 wake as quickly when threatened as drug-free sleepers – and then fall back asleep as quickly as ones given standard sleeping pills, once the threat is gone.Common sleeping pills muffle your sleeping brain’s ‘intruder alert’Even during sleep the brain continuously processes sensory information, waking us if it detects a threat. But the most widely prescribed class of sleeping pills, known as benzodiazepines, makes us less likely to rouse in response to sensory input.”Benzodiazepines stimulate the widespread brain receptor GABA-A, which makes us sleepy but also suppresses off-target brain areas – including the ‘gatekeeper’ that decides which sensory inputs to process,” explains study senior author Professor Tomoyuki Kuwaki of Kagoshima University, Japan.Over the last decade, researchers have been developing a new class of hypnotic drugs called dual orexin receptor antagonists (DORAs). DORAs more selectively target the brain’s sleep/wake pathways, which gives them safety advantages over benzodiazepines. These include a reduced ‘hangover effect’, with DORAs less likely to affect driving ability the day after use.Kuwaki and colleagues hypothesized that the selectivity of DORAs could make them a safer alternative during sleep as well – by allowing the brain’s sensory gatekeeper to stay vigilant to threats.DORA-22 allows mice to wake to a threat, but still helps them sleepThe group tested their theory in mice.The mice were dosed and tested after dark, when they are normally most active. One group was administered 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, extending the duration of deep sleep by 30-40% compared to placebo,” reports Kuwaki.Related StoriesSleep disorders in patients with low back pain linked to increased healthcare visits, costsSleep makes synapses ready for new learningSleep quality could be indicator for later Alzheimer’s disease finds studyOne to four hours after dosing, the deep-sleeping mice were presented with a threatening stimulus: the smell of a fox, a high-pitched noise like a dog whistle, or trembling of their cage. The trembling frequency was designed to match that of an earthquake – a serious threat in Kuwaki’s native Japan and many other parts of the word.”As expected, arousal in response to these threatening stimuli was delayed significantly in the triazolam treatment, but not in the DORA-22 treatment, compared to placebo.Even more promising, the sleep-promoting effect of DORA-22 remained after the rude awakening.”Even though the DORA-22-treated mice were quickly woken by a threat, they subsequently fell back asleep as quickly as with triazolam, and significantly faster than with placebo.”To help demonstrate that the delay in waking to a threat during triazolam treatment was due specifically to inhibition of sensory gating in the brain, the researchers also tested the sleeping mice with a non-sensory stimulus.”The three groups woke equally quickly when we suddenly reduced the amount of oxygen in their cage. This suggests that the delay in rousing to threatening stimuli caused by triazolam was not caused by a general inhibition of waking systems in the brain.”Human studies are needed to confirm DORA safety and efficacy”Although it remains to be seen whether DORAs have the same properties when used in humans, our study provides important and promising insight into the safety of these hypnotics.”Since 2014, another DORA called surovexant has gained regulatory approval in Japan, the USA and Australia. So far, the high cost and limited clinical testing of surovexant have limited its use, amid concerns that doses high enough to significantly improve sleep lead to drowsiness the following day. New DORAs currently in development could overcome this hangover effect if they are cleared more quickly from the body than suvorexant, so that their effects are less likely to last beyond bedtime. Keep your eyes peeled.
Further Reading Source:https://www.sciencedirect.com/science/article/pii/S1871519218306085 By Dr. Ananya Mandal, MDFeb 12 2019A new study has found that because of the stigma around smoking and drinking during pregnancy, many women are doing these in private.Researchers from the University of Cardiff have noted that pregnant women are “irritated and alienated” by the perceived notions regarding the harmful effects of smoking and drinking during pregnancy. Recent figures have shown that one in five women from Wales smoke during their first pregnancy.This new study published in the journal Women and Birth reveals that women feel they receive health advice in a “judgemental tone” from their antenatal healthcare providers and midwives that make them reluctant to open up for advice and support during pregnancy regarding smoking and drinking. Some of the pregnant also reported feeling judged by their non-smoking partners. A significant number of women who were smokers or non-smokers agreed that smoking during pregnancy is acceptable if in private. They however condoned smoking in public. They felt that pregnant women who smoke in public receive a lot of negative judgement and criticism from those around them. E-cigarette smokers too felt judged, the study found.For this study the team of researchers interviewed 10 low income pregnant women belonging to deprived areas of south Wales. They were provided visual questionnaires and clues like timelines, collages and thought bubbles related activities. Image Credit: Napocska / Shutterstock Dr Aimee Grant, from Cardiff University’s Centre for Trials Research, in a statement said, “Moral judgements are commonly directed towards mothers through reference to health behaviour in pregnancy, and working-class mothers are particularly subject to this criticism, ignoring the challenges of living on a low income. Our study shows that these looks and comments – including by members of the public – irritate and alienate pregnant women, making them less likely to seek help. No one wants to be judged and shamed.” The authors of this study called for more “empathy” than judgement.The health advocates worldwide advice pregnant women to abstain from alcohol and smoking tobacco. There are over 4,000 chemicals present in cigarette smoke that can harm the unborn baby and also reduce the oxygen supply. The Chief Medical Officers for the UK makes similar recommendations for pregnant women. The Royal College of Obstetricians and Gynaecologists (RCOG) also added that there are no safe alcohol consumption limits during pregnancy.Dr Dunla Gallagher, one of the co-authors of the study says that smoking could be a “coping strategy” for some of the low-income, pregnant mothers. She said in a statement, “Rather than stigma, women need empathy and a recognition of the challenges that pregnancy can bring in terms of women’s independent choices.” Smoking and Pregnancy Effects of Passive Smoking on Children’s Health Carcinogens in Cigarette Smoke Everything You Need to Know About Giving Up Cigarettes