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.
Carlson
J N
JN
Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA. carlsoj@mail.amc.edu
Haskew
R
R
Wacker
J
J
Maisonneuve
I M
IM
Glick
S D
SD
Jerussi
T P
TP
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