Nistri A, Berti C
Neurosci Lett. 1984 Jun 29;47(3):277-81. doi: 10.1016/0304-3940(84)90526-3.
The isolated frog spinal cord was used as a test system to investigate the interactions of midazolam and caffeine with GABA-evoked responses recorded from dorsal afferent fibres. Midazolam was a potent stimulator (ED50 = 1 nM) of GABA effectiveness on this preparation since the ED50 value for GABA was nearly halved. The enhancing action of midazolam was apparently produced via activation of benzodiazepine receptor mechanisms with no detectable receptor cooperativity and with a rather high sensitivity to the selective benzodiazepine antagonist Ro 14-7437 (antagonist ED50 = 2.5 nM). Responses to glutamate, glycine or high K+ were unchanged in midazolam solutions. When midazolam was applied in concentrations equal or larger than 100 nM, antagonism of GABA responses was evident. Caffeine (50 microM) also potentiated GABA responses through a mechanism distinct from benzodiazepine receptor activation as this action of caffeine was insensitive to Ro 14-7437. Mixtures of low doses of caffeine and midazolam frequently antagonized GABA responses. It is suggested that the blockade of GABA responses by caffeine-midazolam mixtures might account for the reversal of some behavioural actions of these substances even if they probably operate through separate pharmacological mechanisms.
分离的青蛙脊髓被用作测试系统，以研究咪达唑仑和咖啡因与从背根传入纤维记录的GABA诱发反应之间的相互作用。咪达唑仑是这种制剂上GABA效能的强效刺激剂（ED50 = 1 nM），因为GABA的ED50值几乎减半。咪达唑仑的增强作用显然是通过苯二氮䓬受体机制的激活产生的，没有可检测到的受体协同作用，并且对选择性苯二氮䓬拮抗剂Ro 14-7437具有相当高的敏感性（拮抗剂ED50 = 2.5 nM）。在咪达唑仑溶液中，对谷氨酸、甘氨酸或高钾的反应没有变化。当以等于或大于100 nM的浓度应用咪达唑仑时，GABA反应的拮抗作用明显。咖啡因（50 μM）也通过一种不同于苯二氮䓬受体激活的机制增强GABA反应，因为咖啡因的这种作用对Ro 14-7437不敏感。低剂量咖啡因和咪达唑仑的混合物经常拮抗GABA反应。有人提出，咖啡因 - 咪达唑仑混合物对GABA反应的阻断可能解释了这些物质某些行为作用的逆转，即使它们可能通过不同的药理机制起作用。
