Insomia - Ramelteon
Sleep patterns are closely dependent on the body's circadian rhythms. These are the regular variations in physiological parameters that occur over the course of the day, and the principle source of their variation is a group of neurons in the anterior hypothalamus known as the suprachiasmatic nuclei. If the circadian rhythms become distorted then sleep patterns are all too often disrupted.
Sleep patterns are closely dependent on the body's circadian rhythms. These are the regular variations in physiological parameters that occur over the course of the day, and the principle source of their variation is a group of neurons in the anterior hypothalamus known as the suprachiasmatic nuclei. If the circadian rhythms become distorted then sleep patterns are all too often disrupted.
The hormone melatonin is responsible for the synchronisation of the circadian rhythms. It is released by the pineal gland, and its production results from a cascade of signals that occur in response to light levels. The quantity of melatonin in the bloodstream rises and falls through the day along with normal sleep patterns, and its release ultimately leads to the process of falling asleep.
Melatonin can be used to treat sleep disorders, but its bioavailability is not good, and its half-life is only around 15 minutes. Side-effects can also be a problem, because of the unselective nature of its binding to a variety of receptors in the brain. Several analogues have been investigated as potential drug treatments for sleep disorders, and ramelteon, formerly known as TAK-375, is being developed by Takeda.1
In a randomised, double-blind, placebo-controlled Phase II trial in 375 healthy volunteers, the subjects were given a single oral dose of 16 or 64mg of ramelteon or placebo 30 minutes before their normal bedtime, and then monitored for 8 hours by polysomnography.2 Latency to persistent sleep was significantly shorter in those given the active over those given placebo, with no dependence on dose seen; similarly, total sleep time was longer in those given ramelteon than those receiving placebo.
A further Phase II trial has been carried out in patients with primary chronic insomnia. In a randomised double-blind placebo-controlled study, 107 patients were given 4, 8, 16 or 32mg ramelteon or placebo half an hour before normal bedtime for two consecutive nights.3 All groups given active had lower latency to persistent sleep, and total sleep time and sleep efficiency were better, too. There were few 'hangover' after-effects. Trials continue, and the molecule's selectivity and lack of side-effects mean it has great promise as a potential treatment for sleep disorders.