TY - JOUR T1 - Stereoselective discriminative stimulus effects of zopiclone in rhesus monkeys. AU - McMahon,Lance R, AU - Jerussi,Thomas P, AU - France,Charles P, Y1 - 2002/11/14/ PY - 2002/04/01/received PY - 2002/09/20/accepted PY - 2002/11/16/pubmed PY - 2003/5/8/medline PY - 2002/11/16/entrez SP - 222 EP - 8 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 165 IS - 3 N2 - RATIONALE: The behavioral effects of racemic zopiclone are similar to those of benzodiazepines that positively modulate GABA at the GABA(A) receptor complex; however, it is not clear how enantiomers or metabolites of zopiclone contribute to the benzodiazepine-like behavioral effects of racemic zopiclone. OBJECTIVES: Racemic zopiclone, its (R)- and (S)- enantiomers, and the (S)-N-desmethyl metabolite, were evaluated for discriminative stimulus effects in untreated and diazepam treated rhesus monkeys. METHODS: One group of monkeys discriminated the benzodiazepine midazolam and another group, treated daily with the benzodiazepine diazepam (5.6 mg/kg, PO), discriminated the benzodiazepine antagonist flumazenil. RESULTS: (RS)-Zopiclone (0.32-17.8 mg/kg) and (S)-zopiclone (0.1-10 mg/kg) substituted with similar potencies for midazolam (>/=80% midazolam-appropriate responding). The midazolam-like discriminative stimulus effects of (RS)-zopiclone were antagonized by flumazenil (p K(B)=7.52). (R)-Zopiclone occasioned a maximum 45% midazolam-appropriate responding at a dose of 100 mg/kg; (S)-desmethylzopiclone produced saline-appropriate responding up to a dose of 100 mg/kg. All four test compounds occasioned predominantly vehicle-appropriate responding in diazepam treated monkeys discriminating flumazenil. (RS)-Zopiclone (10 mg/kg) attenuated the discriminative stimulus effects of flumazenil in diazepam treated monkeys. CONCLUSIONS: These results clearly demonstrate that in rhesus monkeys the discriminative stimulus effects of zopiclone are stereoselective and qualitatively similar to those of midazolam. These results fail to show any benzodiazepine-like or benzodiazepine antagonist-like discriminative stimulus effects for (S)- N-desmethylzopiclone, suggesting that any behavioral (e.g. anxiolytic) effects of this compound are not the result of actions at benzodiazepine receptors. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/12434260/Stereoselective_discriminative_stimulus_effects_of_zopiclone_in_rhesus_monkeys_ L2 - https://dx.doi.org/10.1007/s00213-002-1286-9 DB - PRIME DP - Unbound Medicine ER -