Chweh A Y, Ulloque R A, Swinyard E A
Eur J Pharmacol. 1986 Mar 18;122(2):161-5. doi: 10.1016/0014-2999(86)90098-1.
The median inhibitory and anticonvulsant potencies of seven benzodiazepine (BDZ) agonists and one BDZ antagonist (Ro15-1788) were established by two tests: inhibition of [3H]flunitrazepam receptor binding and prevention of caffeine-induced seizures in mice. The effect of Ro15-1788 on the anticonvulsant potency of diazepam against caffeine-induced seizures was also investigated. The [3H]flunitrazepam receptor binding inhibitory potencies (IC50s) of the BDZ agonists correlate well with their anticonvulsant potencies (ED50s) against caffeine-induced seizures (r = 0.831; P greater than 0.01 and less than 0.05). Ro15-1788 and clonazepam are the most potent inhibitors (IC50s: 1.72 and 1.75 nM, respectively), but differ markedly in their ability to obtund caffeine-induced seizures (ED50s: 43.2 and 0.226 mg/kg, respectively). Although both Ro15-1788 and diazepam are effective against caffeine-induced seizures, when used in combination Ro15-1788 antagonizes the anti-caffeine effect of diazepam. These data indicate that Ro15-1788 is a BDZ partial agonist with low efficacy as well as a potent antagonist.
通过两项试验确定了七种苯二氮䓬（BDZ）激动剂和一种BDZ拮抗剂（Ro15-1788）的半数抑制和抗惊厥效力：抑制[3H]氟硝西泮受体结合以及预防小鼠咖啡因诱发的惊厥。还研究了Ro15-1788对地西泮抗咖啡因诱发惊厥的抗惊厥效力的影响。BDZ激动剂的[3H]氟硝西泮受体结合抑制效力（IC50）与其抗咖啡因诱发惊厥的抗惊厥效力（ED50）密切相关（r = 0.831；P大于0.01且小于0.05）。Ro15-1788和氯硝西泮是最有效的抑制剂（IC50分别为1.72和1.75 nM），但在抑制咖啡因诱发惊厥的能力上有显著差异（ED50分别为43.2和0.226 mg/kg）。虽然Ro15-1788和地西泮对咖啡因诱发的惊厥均有效，但联合使用时Ro15-1788会拮抗地西泮的抗咖啡因作用。这些数据表明Ro15-1788是一种效力强但疗效低的BDZ部分激动剂，也是一种有效的拮抗剂。
