Benzodiazepine receptor ligands: tools for memory research in clinical pharmacology

In order to study the time course of amnesic effects of the benzodiazepine hypnotic lormetazepam, and their reversal by the benzodiazepine antagonist Ro 15-1788, a combined visual and auditory memory test was developed, which was designed to allow repeated assessments. Immediate recall as well as delayed free recall and recognition (1 h after drug) were investigated before and after intravenous lormetazepam (0.02 mg/kg) followed 15 min later by intravenous Ro 15-1788 (0.03 mg/kg) or placebo. A third group received placebo followed by Ro 15-1788. Results are based on ten subjects per treatment group and are compared with an age-matched control population (n = 20) without treatment. Immediate and delayed recall as well as recognition in both visual and auditory tests were impaired abruptly after intravenous lormetazepam. These effects were reversed instantaneously after Ro 15-1788, which had no marked effect on these parameters when given alone. Ratings by visual analog scales (1 h after drug administration) indicated concomitant sedation and impaired concentration after lormetazepam, which was attenuated by Ro 15-1788. By itself, Ro 15-1788 had no effect on these measures. Interestingly, the performance in delayed free recall of the visual memory test was significantly enhanced in the lormetazepam group prior to administration. Our results suggest that impaired acquisition of new information after lormetazepam is benzodiazepine receptor mediated and may be associated with a drug-induced enhancement of retrieval of information acquired before lormetazepam administration.