THE curse of jet lag has struck most international travellers at one time or another—and anyone lucky enough to have avoided it will surely have suffered the equally unpleasant sleep-deprivation involved in an early-morning start. Nor, as shift workers know too, is it possible to escape by going to bed earlier the previous evening, and thus putting sleep in the bank. Sleepiness is controlled by the body’s internal biological (“circadian”) clock, so an earlier bedtime just means several wakeful hours staring in frustration at a darkened ceiling. A new drug may prevent jet lag
For years, some travellers and shift workers have sworn by melatonin. This is a hormone that regulates the biological clock. It is made in the brain by a structure called the pineal gland, as darkness sets in after sunset. Light is the most potent cue for keeping the biological clock in synch with solar time. The clock then tells the brain when to go to sleep. The theory of those who use melatonin is that an external dose of it can reset the clock, and thus cause the “go to sleep” signal to be sent at a more convenient moment. Melatonin can also increase sleepiness during the day, when the pineal gland is not producing it.
This has resulted in a growing, and often unregulated, market in melatonin-supplement tablets. The pharmaceutical industry’s response to this seems to be: “if you can’t beat ’em, join ’em”. A paper in this week’s Lancet, by Shantha Rajaratnam of the Harvard Medical School and his colleagues, reports two trials, funded by drug companies, of tasimelteon, a substance that binds to the same receptors in the brain as melatonin does, and which it is expected will have a similar effect.
In the course of these trials, more than 400 people had their bedtimes brought forward by five hours in controlled conditions. Half an hour before lights out, a quarter of them were given a placebo, while the remaining three-quarters were given varying doses of tasimelteon.
Dr Rajaratnam and his colleagues report that the new drug let people fall asleep faster at the unnaturally early time, and also allowed them to sleep longer than those given the placebo. Volunteers who took the drug had between 30 minutes and two hours more sleep than those on the placebo, with the largest dose inducing the greatest effect. Physiologically, the drug was observed to advance the body’s natural melatonin-production cycle, and also the pattern of “rapid-eye-movement” sleep, during which most dreaming takes place, and which is believed to be important for the consolidation of memories. Tasimelteon is not, in other words, merely acting as a sedative in the way that benzodiazepines such as diazepam and temazepam do. This is important, says Dr Rajaratnam’s colleague Elizabeth Klerman, because “we want to treat the underlying cause of jet lag or shift-work disorder: the misalignment of the inner circadian clock with the external environmental time.”
It is not only travellers and shift workers who might benefit if tasimelteon leaps all the hurdles that remain before it can be approved. Sleep problems also beset the elderly and the blind. Indeed, one melatonin analogue, called ramelteon, is already used to treat chronic insomnia.
If tasimelteon does pass muster (one gap in these studies is that the daytime effects of taking it, such as the risk of increased sleepiness, have not been looked at) it will be good news for the sleepless. So will the prospect of a simple solution to the melatonin-reducing effects of artificial lighting in rooms and from televisions and computer screens. It turns out that it is the short wavelengths of light (the blues) that are most responsible for fooling the pineal gland into thinking the sun is still above the horizon. It may turn out that a natural way to boost melatonin production is to wear orange glasses in the evening.
Tasimelteon
The Good Drug Guide
info@tasimelteon.co.uk
