'Time-bending drug' for jet lag tasimelteon helps transient insomnia

Tasimelteon is a drug used for the treatment of insomnia and other sleep disorders. It is a selective agonist for the melatonin receptors MT1 and MT2 in the suprachiasmatic nucleus of the brain, similar to older drugs such as ramelteon.

Suprachiasmatic nucleus

The suprachiasmatic nucleus is a tiny region on the brain's midline in a shallow impression of the optic chiasm responsible for controlling circadian rhythms.


The left optic nerve and the optic tracts, suprachiasmatic nucleus not labeled, but diagram illustrates region. Image source: Wikipedia, public domain.

G protein-coupled receptor (GPCR)

A melatonin receptor is a G protein-coupled receptor (GPCR) which binds melatonin. Three types of melatonin receptor have been cloned in humans: MT1 and MT2.

According to the American Chemical Society, "If you had to make a wild guess about the target of a certain drug, your best odds are with “G-protein coupled receptor.” Drugs targeting members of this integral membrane protein superfamily, which transmit chemical signals into a wide array of different cell types, represent the core of modern medicine. They account for the majority of best-selling drugs and about 40% of all prescription pharmaceuticals on the market."

Melatonin receptors agonists

Melatonin receptors ligands (agonists) include:

• Melatonin
• Ramelteon
• Tasimelteon

A bottle of melatonin OTC supplement. Image source: Wikipedia, Ged Carroll, Creative Commons Attribution 2.0 License.

Products containing melatonin have been available as a dietary supplement in the United States since 1993.


Tasimelteon. Image source: Wikipedia, public domain.


Ramelteon, marketed as Rozerem. Image source: Wikipedia, public domain.

Rozerem is the first in a new class of sleep agents that selectively binds to the MT1 and MT2 receptors. Ramelteon caused hyperprolactinaemia 2-3x more often than placebo in clinical trials.

Ramelteon does not bind to GABA receptors, thus it has not been shown to produce dependence, withdrawal and rebound insomnia that is typical with GABA modulators.

Tasimelteon Studies

Circadian rhythm sleep disorders are common causes of insomnia for millions of individuals.

Two recent studies evaluated the efficacy of the melatonin agonist tasimelteon for treatment of transient insomnia associated with shifted sleep and wake time.

Tasimelteon reduced sleep latency and increased sleep efficiency compared with placebo. The frequency of adverse events was similar between tasimelteon and placebo.

The BBC labeled tasimelteon a 'time-bending drug' for jet lag because it can "reset" the body's natural sleep rhythms. Findings would be welcomed by millions of people - "shift-workers, airline crew, tourists, football teams, etc.

Tips for avoiding jet lag

• Sleep well before you travel
• Shift your watch to your destination time zone as soon as you board the plane
• Avoid alcohol
• Spend plenty of time outdoors in the daylight

References:
Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials. The Lancet, Volume 373, Issue 9662, Pages 482 - 491, 7 February 2009.
Tasimelteon, from Wikipedia, the free encyclopedia.
Melatonin receptor, from Wikipedia, the free encyclopedia.
It's a GPCR world. Filmore, David (2004). Modern Drug Discovery (American Chemical Society) 2004 (November): 24–28.
'Time-bending drug' for jet lag. BBC, 2008.

Related reading:

Jet-lagged and forgetful? Memory, learning problems persist long after periods of jet lag http://goo.gl/EPWW6

Coping with Jet Lag. Life in the Fast Lane, 2011.
Jet lag and shift work sleep disorders - CCJM 2011 review.