Sleep disorders almorexant

At least 10% of the population are thought to suffer from insomnia. Drug treatments focus on modulating the GABA receptors, whether the older benzodiazepines, or the more recent drugs zopiclone, zaleplon and zolpidem. While the Z drugs have fewer side effects than the benzodiazepines, they still have their issues.

A different pathway is being investigated by Swiss company Actelion, in collaboration with GlaxoSmithKline the orexins. These are excitatory neuropeptides that are ligands for two different G-protein coupled receptors, OX1 and OX2. The former are believed to be involved in the modulation of REM sleep, and if there are insufficient of the latter, cataplexy can result. The new agent, almorexant, is a dual antagonist of both these receptors, and is being developed as a treatment for sleep disorders.

Several trials have been completed. In a randomised, double blind, placebo and active controlled trial, a total of 70 healthy male subjects were given doses of 1 to 1000mg of almorexant, 10mg zolpidem or placebo.¹ Doses of 400 and 1000mg of the new drug decreased subjective alertness and increased body sway, as did zolpidem, developing about 1 hour after dosing, peaking after 2 hours and lasting for 6 to 8 hours. Almorexant doses of at least 200mg gave a significant, dose-dependent latency to stage 2 sleep, unlike zolpidem or placebo.² The effects of the new drug did not become more pronounced across a four-day dosing period.

A total of 147 subjects with primary insomnia were given 400mg of almorexant or placebo in a randomised, double blind, placebo-controlled, single dose two-way crossover trial.³ The dose was effective at inducing sleep efficiency. The minimum dose to cause a significant increase in sleep efficiency was then determined, and this was achieved at doses down to 100mg. No hangover effects on motor function or reaction time were seen the next day.