Discriminative Stimulus Effects of Benzodiazepine (BZ)1 Receptor-Selective Ligands in Rhesus Monkeys

• DOI: 10.1124/jpet.300.2.505
• Publication Date: 2003-07-27T00:50:36Z
• Authors: Lance R. McMahon; Lisa R. Gerak; Lawrence Carter; Chunrong Ma; James M. Cook; Charles P. France
• Keywords: Flumazenil; Zolpidem; Midazolam; Zopiclone; Inverse agonist

Drug discrimination was used to examine the effects of benzodiazepine (BZ)₁ receptor-selective ligands in rhesus monkeys. In diazepam-treated (5.6 mg/kg, p.o.) monkeys discriminating nonselective BZ antagonist flumazenil (0.32 s.c.), BZ₁-selective β-carboline-3-carboxylate-<i>t</i>-butyl ester (β-CCt) substituted for flumazenil. The onset action β-CCt delayed with a dose 5.6 mg/kg substituting 2 h after injection. agonist midazolam (0.56 agonists zaleplon (ED₅₀ = 0.78 mg/kg) and zolpidem 1.73 midazolam. discriminative stimulus midazolam, zaleplon, were antagonized by (1.0–5.6 also (0.01–0.32 s.c.). Schild analyses supported notion simple, competitive interaction between (slope −1.08; apparent pA₂ 5.41) or −1.57; 5.49) not zolpidem. consistent −1.03; 7.45) −1.11; 7.63). These results suggest that same receptor subtype(s) mediate(s) zolpidem, under these conditions selective binding does necessarily confer vivo.