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Differences between cyclopyrrolones (suriclone and zopiclone) and benzodiazepines bincling to rat hippocampus photolabelled membranes

1983; Elsevier BV; Volume: 32; Issue: 23 Linguagem: Inglês

10.1016/0006-2952(83)90318-0

1873-2968

J.C. Blanchard, Jean‐Luc Zundel, L Julou,

Memory and Neural Mechanisms

The intravenous general anaesthetic propofol (2,6-di-isopropylphenol) is frequently combined with a benzodiazepine. There are clinical reports of synergism between these two agents for induction of general anaesthesia. To investigate a possible mechanism of this synergistic interaction between propofol and benzodiazepines, the effect of propofol and flurazepam on GABAA receptor function was examined in Xenopus occytes expressing human recombinant α1β2γ2L and α2β2γ2L receptor constructs. Potentiation of GABA receptor-activated current by low (1–10 μM) concentrations of propofol together with flurazepam (0.25–0.5 μM) was significantly greater than predicted by an additive response. Isobolographic analysis indicated a strong synergistic interaction between propofol and flurazepam at either of the receptor constructs examined. In contrast, the cyclopyrrolone derivative zopiclone, which produced a similar facilitation of GABA receptor-activated current compared to flurazepam, produced a less than additive potentiation when combined with propofol. Flurazepam significantly decreased the EC50 concentration of propofol for potentiation of GABA responses. Thus, flurazepam, in addition to facilitating GABA receptor activity on its own, also increases the apparent affinity of the GABAA receptor complex to propofol, resulting in a greater than expected potentiation by the combination of propofol plus flurazepam.