Are You Sleeping?


Do you get enough sleep?

This is what happens to your body if it’s deprived of sleep:

  • You have problems with memory and concentration.
  • You have problems finding the right word.
  • You get irritable – you think so?
  • Neurotransmitters in the brain become altered.
  • You become more susceptible to infection.
  • At its extreme, sleep deprivation can lead to death.

h1sciqsleepwalkingIt seems that no matter how many Ambiens (zolpidem) and Lunestas (eszopiclone) we take, we wake up feeling like shit (sorry – there is just no other word!): feeling hung over and inattentive. So much so that the FDA recently cut recommended doses of Ambien and other drugs that contain zolpidem for fear that their use, even the night before, might impair driving or other activities the next day.

This is because Lunesta and Ambien affect GABA receptors, which are found throughout the brain and are associated with side effects, including thinking disturbances, and deficits in attention and memory, explains Jason Uslaner, lead author of a study published in the April 3 issue of Science Translational Medicine.

A new study funded by Merck (of which Uslaner is director of In Vivo Pharmacology at Merck & Co.) has shown that a new class of sleep medications appears to help people fall asleep without causing grogginess the next day (YES! You did read that correctly!)

These new medications – known as dual orexin receptor antagonists (DORA) – target a more specific region of the brain than the other popular sleep drugs, promoting sleep without affecting cognition.

About 15 years ago, scientists discovered chemical messengers known as orexins, which are released by a relatively small brain region known as the lateral hypothalamus. lateralThis area of the brain releases orexins during the day to keep us awake and lowers levels at night so we can sleep.

The appeal of orexin antagonists, said Dr Michael Thorpy, director of the Sleep-Wake Disorders Center at Montefiore Medical Center in New York City, is that they “target a system that’s more specific for sleep.”

That means, theoretically, fewer side effects and perhaps less of a tendency to be habit-forming, Thorpy explained.

Merck already has one such drug, suvorexant, under review by the FDA.

But with this study, Uslaner and his colleagues investigated a compound called DORA-22, which has the same mechanism of action as suvorexant, to see how it fared alongside Ambien, Lunesta and also diazepam (Valium) in rats and rhesus monkeys.

DORA-22 did not lead to the same mental impairments as the other three drugs. Rhesus monkeys and rats performed just as well on memory and attention tasks shortly after being administered DORA-22 as they did on the placebo.

This is the first time in years that scientists have targeted a totally different receptor in the quest to combat insomnia, said Dr Alexandre Abreu, co-director of the UHealth Sleep Center at the University of Miami Miller School of Medicine.

444-36-cartoonBut many questions remain as even experts note that findings from animal studies do not always hold up in human trials: Do the drugs truly have fewer side effects? Will they be habit-forming? And will they change the quality of sleep in any way?

Those questions will only be answered with more testing and use in humans…(waiting…waiting…waiting…)


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Sweet Dreams Ahead?

An investigational insomnia drug, known as suvorexant, is reportedly ‘a new class of drug’ that works in a different way than other sleep meds – and could be THE answer for many of us having difficulty falling asleep or staying asleep through the night.

According to the results of two “pivotal” Phase III effectiveness trials, revealed June 13 at the Associated Professional Sleep Societies annual meeting, suvorexant:

  • Targets insomnia in a different way than other drugs. It was developed to help facilitate sleep by targeting and blocking the actions of the orexins, chemical messengers that originate from the hypothalamus (an important sleep centre in the brain) and help to keep you awake and alert. By blocking the orexin receptors, suvorexant supposedly helps to facilitate sleep.
  • Significantly reduced the time it took insomnia patients to fall asleep and increased the time they stayed asleep as early as the first night and at the three-month time point, compared to placebo.
  • Produced no serious observed drug-related adverse events in either trial with any dose of suvorexant. Reports of next day residual effects on memory, attention, perceptual & motor speed, etc. were not significantly more frequent in treated subjects vs. those given placebo.

Merck plans to file a New Drug Application (NDA) for suvorexant with the US FDA in later this year. If approved, it would be the first medicine approved in the new class of medicines – called ‘orexin receptor antagonists,’ for use in patients with difficulty falling or staying asleep. If approved, it could be your dream come true!