Product Details

ZOPICLONE

Chemical group—
    Cyclopyrrolone derivative.
Molecular weight—
    388.82.

Solubility
    Freely soluble in chloroform and methylene chloride; soluble in dimethylformamide and 0.1 N hydrochloric acid; slightly soluble in acetone; nearly insoluble in water, ethanol, or ethyl ether.

Mechanism of action/Effect:

Zopiclone is a non-benzodiazepine hypnotic agent, with marked sedative effects. Although unrelated chemically to the benzodiazepines, it produces similar pharmacological effects.

Although the precise mechanisms have not been completely established, the activity of zopiclone is believed to be related to its binding on the benzodiazepine receptor complex and facilitation of the gamma-aminobutyric acid (GABA) function. It does not appear to bind to sites corresponding exactly to benzodiazepine sites, but rather to sites close by on the receptor complex. Enhanced binding of GABA to the GABA-chloride ionophore complex occurs to a greater extent with benzodiazepines as compared to zopiclone. Zopiclone lacks affinity for the serotonin, GABA1 and GABA2 adrenergic, and dopamine receptors.


Other actions/effects:

In animal studies, zopiclone has demonstrated other central nervous system activity, including anticonvulsant, muscle-relaxant, anti-aggression, and anxiolytic properties.{01}{02} The drug potentiates narcosis induced by ethanol or barbiturates.{01}

Absorption:

Rapidly and well absorbed; >75% bioavailability.{01}

Distribution:

Zopiclone is distributed into human breast milk; its concentration is approximately 50% that of plasma concentrations.{01}

Protein binding:

Moderate (approximately 45%).{01}

Biotransformation:

Extensively metabolized in the liver via decarboxylation (major pathway), demethylation, and side chain oxidation. Metabolites include an N-oxide derivative (weakly active; approximately 12% of a dose) and an N-desmethyl metabolite (inactive; approximately 16%). Approximately 50% of a dose is converted to other inactive metabolites via decarboxylation. Hepatic microsomal enzymes are apparently not involved in zopiclone clearance

Precautions to Consider

Carcinogenicity/Tumorigenicity

An increased incidence of mammary tumors and pulmonary adenocarcinomas occurred in female rats and mice given 100 milligrams of zopiclone per kg of body weight (mg/kg) per day for 2 years{01} In male rats and mice receiving the same high doses, an increased incidence of thyroid and subcutaneous soft tissue tumors was observed.{01}The tumor-producing dose was equivalent to 800 times the usual human dose (0.125 mg/kg), and no effect occurred with doses that were 80 times the usual human dose.{01}

Mutagenicity

Zopiclone showed no evidence of mutagenicity in a wide battery of tests.{01} Urine extracts from zopiclone-treated mice, rats, and humans were not mutagenic.{01} No evidence of mutagenicity was found in the DNA repair assay in rat hepatocytes (William's test), in the Ames test in Salmonella typhimurium and Escherichia coli strains, or in the micronucleus test (mice).{01}

Pregnancy/Reproduction
Fertility—
In rat studies, zopiclone did not affect fertility in doses up to 12 mg/kg.{01} Sterility was induced in male rats given zopiclone 120 mg/kg for 10 weeks prior to mating.{01} Pregnancy rates were slightly lower in female rats given 120 mg/kg for 2 weeks prior to mating (83% compared with 100% in controls).{01} Survival rates were also lower in fetuses of female rats that received zopiclone (120 mg/kg for 2 weeks prior to mating , during pregnancy, and during lactation) than in fetuses of controls. {01}

Pregnancy—
Insufficient data are available to assess the safety of zopiclone during human pregnancy.

Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Confusion — higher incidence in the elderly{01}
    
daytime anxiety and/or restlessness
    
impaired coordination (clumsiness or unsteadiness; difficulty with coordination)—higher incidence in elderly{01}
    
mental depression (mood or mental changes){01}
{01}
Note: Daytime anxiety and/or restlessness may be a manifestation of interdose withdrawal, due to the short elimination half-life of zopiclone.{01}


Incidence less frequent
    
Drowsiness (severe) {01}
    
dyspnea (shortness of breath ; difficult or labored breathing; tightness in chest; wheezing){01}
    
skin rash {01}
    
unusual behavior{01}, including aggressiveness{01}
and extroversion{01} (behavior or mental changes)

{01}
Note: Skin rash may be a sign of hypersensitivity to zopiclone. The medication should be discontinued if a skin rash appears.{01}



Incidence Rare
    
Anterograde amnesia{01} (memory problems)
    
disturbed thinking, including abnormal thoughts
depersonalization
hallucinations

SOURCE: DRUGS.COM