Eszopiclone

Eszopiclone is a non-benzodiazepine hypnotic agent indicated for the treatment of insomnia to induce sleep and for sleep maintenance. It has similar pharmacokinetic and pharmacodynamic parameters as the previously marketed non-benzodiazepine hypnotics zolpidem and zaleplon. However, unlike its predecessors, eszopiclone is not restricted to short-term treatment of insomnia. Clinical studies of up to 6 months of use show that patients do not develop tolerance to its effect. Eszopiclone is the (S)-enantiomer of zopiclone, which has been marketed as the racemic mixture in Europe for almost 20 years. These agents belong to the cyclopyrrolone class of drugs that act as agonists at the type A GABA receptor. Eszopiclone has approximately 50-fold higher binding affinity than its antipode (R)-zopiclone for GABA-A receptor (IC₅₀=21 and 1130 nM, respectively). In addition, the two enantiomers exhibit significant differences in their pharmacokinetic parameters and in vivo efficacy. In healthy volunteers, eszopiclone has 2-fold higher C_max and 2-fold greater elimination half-life than the (R)-enantiomer.The two most frequent adverse events associated with eszopiclone treatment are unpleasant taste and headache. Other less frequent side effects include somnolence, dry mouth, and nausea.