A study in rats and monkeys
suggests an experimental Merck & Co sleep drug may help
induce sleep without causing the memory loss and attention
problems sometimes seen in the commonly used drugs Ambien and
Lunesta, company researchers said.
Experiments in animals suggest Merck's sleep drug
Suvorexant, now before the US Food and Drug Administration,
may avoid these side effects, the company said.
Insomnia affects about 10% of US adults, and
roughly a third of these individuals take drugs to help them
sleep. Most sleep aids, including Sanofi's Ambien or
Sunovion Pharmaceuticals' Lunesta, act on a key neurotransmitter
in the brain called GABA.
"These treatments work by forcing the brain to go to sleep,"
said study leader Jason Uslaner of Merck in an interview on the
website of Science Translational Medicine, which published the
Sleep can cause memory loss
GABA receptors are important to many brain regions,
including those important for cognition, which is likely why
common sleep aids can cause memory loss and attention problems.
"When you hit those, you don't just hit the sleep system,"
John Renger, executive director and head of neruoscience basic
research at Merck and one of the study's authors, said in a
Suvorexant is part of a class of drugs called Dual Orexin
Receptor Antagonists or DORAs, which work by blocking chemical
messengers called orexins. Orexins are responsible for keeping
people awake. Levels of this compound rise during the day and
fall at night.
Orexins originate in a specific region of the hypothalamus,
so targeting them may have less impact on other brain functions,
For this study, the team wanted to find out what would
happen if someone is awakened on this drug and has a very high
level of it in their system.
"How impaired would they be?" Renger said.
How the study was done
To test this, the researchers did a series of experiments on
rhesus monkeys and rats. First, the team trained monkeys to
perform a common attention test in which they needed to respond
quickly to a blinking light on a screen and remember what they
touched. Monkeys given GABA inhibitors were much slower in
responding to the prompt, and in some cases, missed it
altogether, while monkeys given a potent orexin blocker called
DORA-22 did not show these attention issues, Renger said.
The team also saw differences in a simple memory test in
rats. Rats were first exposed to a colored object, and then
later exposed to it again. Typically, rats that recall an object
show less interest in it when they are shown it again.
In the study, rats given GABA blockers were less likely to
recall the objects than those given DORA-22.
Emmanuel Mignot of Stanford University, who wrote a
commentary on the study in the same journal, said the findings
"Are DORAs the perfect hypnotics? Only long-term use in
large numbers of insomnia patients will reveal whether these
drugs will be preferred to GABAergic hypnotics, and whether they
produce rare complications, including narcolepsy-like symptoms
in predisposed individuals," Mignot wrote.
So far, Merck has not seen any cases of narcolepsy, a sleep
disorder marked by daytime sleepiness, in its late-stage
clinical trials, Renger said.
The most common side effects from Suvorexant have been
headache and sleepiness. No serious drug-related side effects
have been reported.