Zopiclone/Lunesta relationship

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SUPPLEMENTARY INFORMATION: Zopiclone is a central nervous system depressant drug. On December 15, 2004, the Food and Drug Administration (FDA) approved (S)-zopiclone (or eszopiclone), the active (S) isomer of zopiclone, for marketing under the trade name LunestaTM. Eszopiclone will be marketed as a prescription drug product for the short-term treatment of insomnia.

Racemic (R, S) zopiclone, commonly known as zopiclone, is a pyrrolopyrazine derivative of the cyclopyrrolone class and is a mixture composed of equal proportions of two optical isomers identified as (S)- zopiclone (or eszopiclone) and (R)-zopiclone. Its chemical name is 1- piperazinecarboxylic, 4-methyl-, (5RS)-6-(5-chloro-2-pyridinyl)-6,7- dihydro-7-oxo-5H-pyrrolo [3,4-b]pyrazin-5yl ester (CAS number 43200-80- 2). Eszopiclone is the most active component of the racemic (R,S) zopiclone.

Zopiclone and its (S) and (R) forms of optical isomers share with benzodiazepines (e.g. diazepam) substantial similarities in their pharmacological properties such as anxiolytic, sedative and hypnotic actions. In controlled clinical studies, zopiclone has been found to be superior to placebo on subjective measures of sleep latency and total sleep time. In healthy human subjects, eszopiclone is rapidly absorbed with a time to peak concentration (tmax) of approximately 1 hour following oral ingestion (1-7.5 mg) and has an elimination half-life (t[frac1s2]) of approximately 6 hours.

In clinical trials, eszopiclone shows an adverse event profile comparable to that of other hypnotics. Some adverse effects of eszopiclone include hallucinations, amnesia, difficulty concentrating, memory impairment, depression, somnolence and accidental injury.

The abuse potential of zopiclone and its optical isomers is similar to those of the benzodiazepines and the nonbenzodiazepine hypnotics, zaleplon and zolpidem, that are all currently listed in Schedule IV of the CSA. It produces euphoria, alterations in mood, perception, memory and subjective effects in humans typical of other benzodiazepines with abuse potential in Schedule IV. Zopiclone is positively reinforcing in monkeys. Zopiclone generalizes to the discriminative stimulus effects of zolpidem and benzodiazepines such as diazepam, chlordiazepoxide, and midazolam in animals. Conversely, benzodiazepines, namely diazepam, nitrazepam and alprazolam, generalize to stimulus effects of zopiclone in animals.

Case reports of dependence and withdrawal effects to zopiclone have been published in the scientific literature. Some symptoms of zopiclone withdrawal include insomnia, anxiety, tremors, palpitations, and craving. Clinical trials indicate that withdrawal effects from eszopiclone are similar to those of benzodiazepines.