Hypnotic - eszopiclone
Lack of sleep is a major health problem in the developed world. The body needs sleep to function properly, yet as many as 35% of western adults are estimated to have some difficulty in sleeping. Drugs have been used to induce sleep since time immemorial. The pharmaceutical industry has been making sleeping medicines since the introduction of chloral hydrate in the 1860s, and the benzodiazepines later revolutionised the treatment of insomnia. Modern medicines have much reduced side-effect profiles from the benzodiazepines, and addiction is much less of an issue.
Zopiclone, one of these modern medicines, is racemic, and the S-isomer, eszopiclone, is undergoing trials by Sepracor.1 Like other hypnotics, it acts at the GABAA receptors, and the S-isomer has a much greater affinity for the receptors than the R form.
In a trial in 308 patients with chronic insomnia, subjects were given 2 or 3mg of eszopiclone or placebo for six weeks.2 Its efficacy and rebound insomnia potential were measured, and both doses were found to give much better sleep onset than placebo. Sleep lasted for longer and was better maintained, and no residual daytime effects were seen. It was well tolerated, with the most common side-effect reported being an unpleasant taste.
A further multicentre trial was carried out in 788 chronic insomnia sufferers. Patients were given 3mg eszopiclone or placebo every night for six months.3 Again, those given eszopiclone had much better sleep maintenance and quality of sleep. There were no signs of tolerance, and after the trial had finished, patients were able to continue taking the medicine for a further six months in an open label study.
At the end of this period, there was still no evidence of tolerance, and its effectiveness was not lost. And those given the drug had better daytime alertness and functioning over the year than those given placebo.
Eszopiclone has been submitted to the FDA for approval. Unlike in Europe, where it has been marketed successfully for many years and is now available in generic form, racemic zopiclone has never been available in the US, so it has great potential for making a successful chiral switch.