Sedative and anxiolytic effects of zopiclone's enantiomers and metabolite.
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.
Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA. carlsoj@mail.amc.edu
J N
JN
Carlson
R
R
Haskew
J
J
Wacker
I M
IM
Maisonneuve
S D
SD
Glick
T P
TP
Jerussi
D000525:Alprazolam / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy; D053961:Azabicyclo Compounds; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D006993:Hypnotics and Sedatives / Q000494:pharmacology* / Q000627:therapeutic use; D007536:Isomerism; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009048:Motor Skills / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D012640:Seizures / Q000188:drug therapy
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone; C053229:N-desmethylzopiclone; D003975:Diazepam; D000525:Alprazolam