Intrinsic Activity of the Benzodiazepine Antagonist Ro 15-1788 in Man: An Electrophysiological Investigation

Abstract

Ten healthy volunteers were injected i.v. with 5 mg Ro 15-1788, a specific benzodiazepine antagonist, or placebo in a double-blind randomised design. In the EEG, Ro 15-1788 led--with some topographical variations--to a diminution of theta and alpha power, an increase of alpha mean frequency and a decrease of delta mean frequency. In auditory evoked potentials, the N1P2 and P2N2 amplitudes decreased. The electrophysiological changes induced by Ro 15-1788 are consistent with a central stimulant action. Ro 15-1788 induced some slight behavioural and subjective changes.

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

“…Flumazenil did not affect the risk assessment measures, but it dramatically potentiated flight reactions while weakly, albeit significantly, reducing defensive aggression and contextual anxiety. The effects of flumazenil on flight may well fit with clinical observations that the drug is somewhat anxiogenic in healthy volunteers (Darragh et al, 1983;Duka et al, 1986;Schopf et al, 1984) and that it increases the frequency of panic attacks in panic disorder patients (Maddock, 1998;Nutt et al, 1990;Woods et al, 1991). The weak agonist-like activity of flumazenil on defensive aggression is at first glance surprising, but it may fit with the idea that the drug can produce a GABA A -benzodiazepine receptor set point shift either toward the agonistic or the inverse agonistic direction, depending on the aversiveness of the situation (Belzung et al, 2000).…”

Mouse defensive behaviors: pharmacological and behavioral assays for anxiety and panic

“…imipramine,¯uoxetine, moclobemide and phenelzine), reduced¯ight behavior [12,48,49,51]. In contrast, drug challenges known to trigger or potentiate human panic responses such as acute imipramine,¯uoxetine, yohimbine or the BZ receptor antagonist¯umazenil [27,54,55,90] were found to increase¯ight [16,48]. Also in agreement with clinical data are the ®ndings that the traditional BZ chlordiazepoxide, the 5-HT1A receptor agonist buspirone and the 5-HT2 receptor antagonist mianserin did not modify¯ight behavior in this test [50,52].…”

Possible interaction of fluoroquinolones with the benzodiazepine‐GABAA‐ receptor complex.

“…Whereas in some studies (Doenicke et al, 1984, Gath et al, 1984Noderer et al, 1988) no significant changes compared with placebo were reported, Schopf et al (1984) found with 5 mg flumazenil a similar central stimulant action to that described above. Furthermore, Ziegler et al (1985) could demonstrate that flumazenil (10 mg i.v.)…”