A double-dissociation of behavioural and event-related potential effects of two benzodiazepines with similar potencies

Abstract

This study was designed to explore the role of benzodiazepine affinity to benzodiazepine binding site on acute psychomotor, subjective and memory effects, as well as auditory Event Related Potential (ERP) latencies, in healthy volunteers. Two benzodiazepines with similar affinity to benzodiazepine binding sites, or potency, were compared: the atypical compound lorazepam (2.0 mg), which has been reported to impair priming, and a standard benzodiazepine, flunitrazepam (0.6 mg, 0.8 mg, 1.0 mg). The study followed a placebo-controlled, double-blind, parallel-group design. Sixty subjects completed a test battery before treatment and at theoretical peak plasma concentration of drugs. Lorazepam and 1.0 mg of flunitrazepam led to comparable alterations on psychomotor, subjective and auditory episodic memory measures. A double-dissociation was found for lorazepam and the equipotent dose of flunitrazepam (1.0 mg): lorazepam was more deleterious than flunitrazepam in time taken to identify fragmented shapes. Lorazepam also impaired direct and indirect stem-completion in comparison to placebo, but this effect was abolished when time to identify shapes was used as a covariate. By contrast, 1.0 mg of flunitrazepam prolonged auditory ERP latencies to a greater extent than lorazepam. High affinity to the benzodiazepine binding sites does not seem to explain the consistent lorazepam-induced impairment of indirect stem-completion. Differences in impairment profile between the benzodiazepines employed may relate to the modality (visual or not) of the tasks used.