Byrnes J J, Greenblatt D J, Miller L G
Department of Pharmacology and Experimental Therapeutics and Psychiatry, Tufts University School of Medicine, Boston, MA.
Brain Res Bull. 1992 Dec;29(6):905-8. doi: 10.1016/0361-9230(92)90164-s.
Several classes of nonbenzodiazepine compounds, including imidazopyridines such as alpidem and zolpidem and cyclopyrrolones, e.g., zopiclone, have effects similar to benzodiazepines and may act at the benzodiazepine receptor in brain. We characterized the binding of these compounds to the benzodiazepine site in three brain regions using specific uptake of the high-affinity ligand [3H]Ro15-1788 (flumazenil). For alpidem, benzodiazepine binding was decreased in cortex and hippocampus with increasing drug dose. For zolpidem, receptor binding was reduced in cortex without a dose-response effect and no effect was observed on cerebellar binding. Zopiclone did not alter binding except for a decrease in binding at the lowest dose evaluated and an increase in binding above control at the highest dose. These data corroborate prior studies indicating that the imidazopyridines appear to act at the benzodiazepine receptor, but do not support receptor subtype selectivity of zolpidem. The limited effect of zopiclone except for increased binding at high doses is also consistent with prior studies suggesting that zopiclone acts at a site distinct from the benzodiazepine receptor.
几类非苯二氮䓬化合物，包括咪唑吡啶类如阿吡坦和唑吡坦以及环吡咯酮类如佐匹克隆，具有与苯二氮䓬类相似的作用，且可能作用于脑内的苯二氮䓬受体。我们使用高亲和力配体[3H]Ro15 - 1788（氟马西尼）的特异性摄取来表征这些化合物在三个脑区与苯二氮䓬位点的结合。对于阿吡坦，随着药物剂量增加，皮质和海马中的苯二氮䓬结合减少。对于唑吡坦，皮质中的受体结合减少，但无剂量反应效应，且在小脑结合上未观察到影响。除了在评估的最低剂量下结合减少以及在最高剂量下结合高于对照增加外，佐匹克隆未改变结合。这些数据证实了先前的研究，表明咪唑吡啶类似乎作用于苯二氮䓬受体，但不支持唑吡坦的受体亚型选择性。佐匹克隆除了在高剂量下结合增加外的有限作用也与先前的研究一致，表明佐匹克隆作用于与苯二氮䓬受体不同的位点。
