Sedative and anxiolytic effects of zopiclone's enantiomers and metabolite.

Abstract

We evaluated racemic zopiclone, its (S)- and (R)-enantiomers and a metabolite, (S)-desmethylzopiclone, for their actions on locomotor activity, rotarod performance, the elevated plus maze and the Vogel conflict test of anxiety, and electroconvulsive shock-induced seizures duration. Zopiclone and its (R)- and (S)-enantiomers reduced locomotor activity, and zopiclone and its (S)-enantiomer disrupted rotarod performance at 10 mg/kg. (S)-desmethylzopiclone did not alter these measures at doses of less than 200 mg/kg. (S)-desmethylzopiclone altered plus maze performance at the lowest dose of all the zopiclone derivatives tested, caused a dose-related effect on the Vogel conflict test and caused a dose-related reduction of electroconvulsive shock-induced seizure durations. The data indicate that (S)-desmethylzopiclone can bring about an anxiolytic effect without a substantial degree of central nervous system depression, and suggest that the agent may be particularly useful clinically in the treatment of anxiety.

• Authors: J N Carlson, R Haskew, J Wacker, I M Maisonneuve, S D Glick, T P Jerussi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 415 Issue 2-3 Pg. 181-9 (Mar 2001) ISSN: 0014-2999 [Print] Netherlands
• PMID: 11274997 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Anxiety Agents
• Anticonvulsants
• Azabicyclo Compounds
• Hypnotics and Sedatives
• Piperazines
• zopiclone
• N-desmethylzopiclone
• Diazepam
• Alprazolam

Topics

• Alprazolam (pharmacology)
• Animals
• Anti-Anxiety Agents (pharmacology, therapeutic use)
• Anticonvulsants (pharmacology, therapeutic use)
• Anxiety (drug therapy)
• Azabicyclo Compounds
• Diazepam (pharmacology)
• Dose-Response Relationship, Drug
• Electroshock
• Hypnotics and Sedatives (pharmacology, therapeutic use)
• Isomerism
• Male
• Motor Activity (drug effects, physiology)
• Motor Skills (drug effects, physiology)
• Piperazines (chemistry, pharmacology, therapeutic use)
• Rats
• Rats, Long-Evans
• Seizures (drug therapy)