Merck Plans To File Insomnia Drug Application To FDA In 2012

[23536]

Merck & Co. (MRK) said Monday that it plans to apply this year for U.S. regulatory approval to market a potential new treatment for insomnia, based on positive clinical-trial results.

The experimental drug, suvorexant, uses a new mechanism designed to help people sleep while potentially mitigating side effects associated with existing sleep aides. Some analysts estimate annual sales of the drug could top $500 million within several years.

. . .

Suvorexant, formerly code-named MK-4305, is known as an orexin receptor antagonist. Orexin is a neuropeptide in the brain that plays a role in promoting wakefulness. Suvorexant is designed to block the effect of orexin in the brain, promoting sleep in insomniacs.

It's a different approach than older insomnia drugs known as benziodiazepines, as well as newer drugs like Sanofi's (SNY, SAN.FR) Ambien, which target so-called GABA receptors found throughout the brain. These drugs essentially depress the central-nervous system, but they can lead to dependence or have withdrawal effects, such as drowsiness in the morning.

Suvorexant is designed to target the orexin receptors in one small portion of the brain, temporarily switching off the brain's arousal symptom but avoiding the depression of the central nervous system.

Merck's development of suvorexant was partly based on studies of very sleepy dogs, or canine narcolepsy. Research conducted more than a decade ago by scientists, including Emmanuel Mignot of Stanford School of Medicine, found a genetic mutation in dogs associated with narcolepsy. Further research found that the mutation was linked to orexin, and that this link was present in humans as well.


Read more: http://www.foxbusiness.com/news/201...rug-application-to-fda-in-2012/#ixzz1ld3SqlnD

 

[NeighborhoodThreat]

Interesting, a novel method of action...

 

[DexterMeth]

This sounds promising.

 

[cj]

hmm I wondeer what kind of withdrawl effects they are talking about? Would this have recreational potential? Finally would it be useful for anxiety? Im just wondering if this will be the end of benzos as frontline drugs?

 

[paranoid android]

Benzos have so many different uses and doctors are so familiar with them that there is no way they are going anywhere. A drug that helps sleep may not help anxiety that much either which is what i found zopiclone and zaleplon to be like. So i wouldn't worry about your benzo script going anywhere soon

 

[23536]

Would this have recreational potential? Finally would it be useful for anxiety?

The agonists do (nsfw for length):

NSFW:

Sleep hormone restores vigor and reverses apathy in sickness, Oregon scientists report

Getting sick can make anyone fell listless and blah, and some chronic conditions leave people feeling that way all the time.

Now Portland scientists have found a way to reverse such illness-induced lethargy. They used a naturally occurring brain hormone called orexin, already known to be pivotal in regulating sleep in people, to restore normal activity in laboratory animals.

The research shows how it may be possible to make a pill to restore vigor in people suffering from chronic fatigue and apathy brought on by cancer, congestive heart failure, kidney disease, and many other conditions – without the side-effects of stimulants such as caffeine or amphetamines.

"The basic biology suggests it would be broadly applicable to a variety of disease states," says Dr. Daniel Marks, an associate professor of pediatrics at Oregon Health & Science University and scientist in the Papé Family Pediatric Research Institute.

The findings open a new window on the brain's primary system controlling sleep and alertness. Orexin hormones were discovered in the late 1990s. Orexin promotes arousal from sleep when it binds to sensitive brain cells. Blocking orexin signals in the brain induces sleep. Loss of orexin is the primary cause of the severe sleep disorder narcolepsy.

"In more than 90 percent of those patients, orexin neurons are either killed or completely inactivated," says Dr. Masashi Yanagisawa, a professor at the University of Texas Southwestern Medical Center in Dallas, whose lab discovered orexin hormones.

Marks and colleagues at OHSU used laboratory rats to find out whether orexin also serves as the master controller of the lethargy that comes with sickness. The researchers used a well-established illness model, in which doses of a bacterial toxin trigger typical sickness behavior in rats, including a lot of lying around doing nothing.

During the simulated infection, the researchers measured orexin levels in the rats' spinal fluid. They found that orexin plummeted as the rats became more listless. Marks said the immune system's response to infection starts a chain reaction of inflammation that ultimately turns off the brain cells that release orexin. Deprived of the hormone, the animals lose the motivation to move.

But when researchers replenished orexin with infusions, the listless animals became active. Researchers mounted micro tracking devices that measured the rats' movements. They also videotaped the animals around the clock to track the quality of their activity.

"They were walking around, exploring and grooming themselves," says Marks. "It was normal, get-off-the couch kind of behavior."

Marks says the study shows how a pill that mimics orexin could theoretically help chronically ill patients regain function, live more independently and feel more vigorous. He says drug companies have already begun developing orexin-like drugs because of the hormone's well-established role in narcolepsy and other sleep disorders. The researchers published their findings in The Journal of Neuroscience.

. . .

Marks and others are mindful of the potential for orexin drugs to be abused, or used in ways that raise troubling ethical questions. For instance, Marks is uncomfortable with the idea of the potential military application of orexin drugs to keep soldiers fighting in spite of illness or lack of sleep. He says livestock producers could use orexin drugs to mask signs of illness in cattle, pigs and other animals headed for slaughter.

http://www.oregonlive.com/health/index.ssf/2011/08/sleep_hormone_restores_vigor_a.html

It's not impossible that the antagonists trigger upregulation of orexin or orexin receptors while you sleep. I'm pretty sure I've read something about that very thing.

 

[Geaux Tigers!]

Hmm, I imagine this will be a subtle Ramelteon feel to it; likely not too recreational. There has to be something to it in terms of promoting sleep or it wouldn't have got the greenlight by Merck. I imagine that it'd take a lot more to get some Bluelighters here to sleep...