Differential interactions between benzodiazepines and the dihydropyridines, nitrendipine and Bay K 8644
Differential interactions between benzodiazepines and the dihydropyridines, nitrendipine and Bay K 8644
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DOI：
10.1016/0028-3908(91)90148-5
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发表时间：
1991-03
影响因子：
4.7
通讯作者：
S. Dolin;T. Patch;M. Rabbani;P. Taberner;H. Little
中科院分区：
文献类型：
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作者：
S. Dolin;T. Patch;M. Rabbani;P. Taberner;H. Little
比较了二氢吡啶类钙拮抗剂尼群地平和钙通道激活剂 Bay K 8644 与苯二氮卓类药物的麻醉、共济失调和抗惊厥作用。还检查了外周苯二氮卓受体拮抗剂 PK11195 和经典苯二氮卓类药物之间可能存在的相互作用。尼群地平显着增强苯二氮卓类药物的麻醉作用并增加其共济失调作用，但对抗惊厥作用没有影响。氯硝西泮剂量高达 1 g kg−1 或与尼群地平合用时不会产生麻醉作用。单独给药时，尼群地平不会引起全身麻醉。尼群地平似乎不会改变咪达唑仑的代谢。钙通道激活剂 Bay K 8644 会降低咪达唑仑的麻醉效力，单独给药时会产生共济失调。它没有显着改变咪达唑仑的中心浓度。 “外周”苯二氮卓类拮抗剂 PK11195 不影响苯二氮卓类药物的共济失调或麻醉作用。这些结果表明，二氢吡啶敏感的钙通道可能对全身麻醉比苯二氮卓类药物的抗惊厥作用更重要。 “外围”苯二氮卓位点似乎在这两个特性中都没有发挥作用。
The effects of the dihydropyridine calcium antagonist, nitrendipine and the calcium channel activator, Bay K 8644, have been compared on the anaesthetic, ataxic and anticonvulsant effects of benzodiazepines. Possible interactions between the peripheral benzodiazepine receptor antagonist, PK11195, and the classical benzodiazepines were also examined.Nitrendipine considerably potentiated the anaesthetic effects of benzodiazepines and increased their ataxic effects but had no effect on the anticonvulsant actions. Clonazepam did not produce anaesthesia, at doses up to 1 g kg−1or when given with nitrendipine. When given alone, nitrendipine did not cause general anaesthesia. Nitrendipine did not appear to alter the metabolism of midazolam.The calcium channel activator, Bay K 8644, reduced the anaesthetic potency of midazolam and, when given alone, produced ataxia. It did not significantly alter central concentrations of midazolam. The “peripheral” benzodiazepine antagonist, PK11195, did not affect the ataxic or anaesthetic actions of benzodiazepines.These results suggest that dihydropyridine-sensitive calcium channels may be more important to the general anaesthetic than to the anticonvlsant actions of benzodiazepines. The “peripheral” benzodiazepine site did not appear to play a role in either of these properties.