Forster A, Juge O, Louis M, Nahory A
Anesth Analg. 1987 Apr;66(4):309-13.
RO 15-1788, a specific benzodiazepine antagonist, although it effectively antagonizes the clinical effects of benzodiazepines (i.e., sedation and amnesia), can also induce subjective agonist effects such as sedation or inverse agonist effects such as anxiety. The purpose of this study was to investigate in seven healthy volunteers the effect of RO 15-1788 on cerebral blood flow when intravenously injected alone or with midazolam and to compare its effects with midazolam administered alone. Cerebral blood flow was measured with the 133xenon inhalation technique and the drugs were administered simultaneously in a double-blind, randomized fashion during the four following sessions: placebo-placebo; midazolam-placebo; RO 15-1788-placebo; midazolam-RO 15-1788. No difference in cerebral blood flow was noted between the placebo-placebo, the RO 15-1788-placebo, and the RO 15-1788-midazolam sessions--although midazolam injected alone decreased cerebral blood flow by 30%. The sedation, amnesia, and the electroencephalograph (EEG) and muscle tone changes observed with midazolam-placebo were not present during the RO 15-1788-placebo and RO 15-1788-midazolam sessions. This study demonstrates the absence of effects of RO 15-1788 on cerebral blood flow when injected alone and the efficacy of this new drug in antagonizing the depressant effects of midazolam on cerebral hemodynamics.
RO 15 - 1788是一种特异性苯二氮䓬拮抗剂，尽管它能有效拮抗苯二氮䓬类药物的临床效应（如镇静和失忆），但也能诱发主观激动剂效应（如镇静）或反向激动剂效应（如焦虑）。本研究的目的是在7名健康志愿者中，研究单独静脉注射RO 15 - 1788或与咪达唑仑联合使用时对脑血流量的影响，并将其效应与单独使用咪达唑仑的效应进行比较。采用133氙吸入技术测量脑血流量，在以下四个阶段以双盲、随机方式同时给药：安慰剂 - 安慰剂；咪达唑仑 - 安慰剂；RO 15 - 1788 - 安慰剂；咪达唑仑 - RO 15 - 1788。在安慰剂 - 安慰剂、RO 15 - 1788 - 安慰剂和RO 15 - 1788 - 咪达唑仑阶段之间，未观察到脑血流量有差异——尽管单独注射咪达唑仑会使脑血流量降低30%。在RO 15 - 1788 - 安慰剂和RO 15 - 1788 - 咪达唑仑阶段，未出现咪达唑仑 - 安慰剂阶段所观察到的镇静、失忆以及脑电图（EEG）和肌张力变化。本研究表明，单独注射RO 15 - 1788对脑血流量无影响，且这种新药能有效拮抗咪达唑仑对脑血流动力学的抑制作用。
