Effects of lorazepam on memory, attention and sedation in man: antagonism by Ro 15-1788.
In this study we examined the effects of lorazepam (2.0 mg PO) plus either placebo or one of three doses of the benzodiazepine antagonist Ro 15-1788 (0.3 mg, 1.0 mg or 3.0 mg IV) on measures of memory, attention and sedation. We found that lorazepam impaired verbal secondary memory performance, but also produced subjective and objective sedation; it increased reaction time, reduced critical flicker fusion thresholds and caused subjects to make more errors on a sustained attention task and rate themselves as drowsy. Ro 15-1788 dose dependently blocked the deficit in secondary memory produced by lorazepam, but also showed monotonic dose-related antagonism of its effects on indices of sedation (with the exception of the critical flicker fusion deficit, which was unaffected). These results demonstrate that lorazepam-induced cognitive deficits can be blocked by a benzodiazepine receptor antagonist. They also suggest that the memory deficits produced in this pharmacological model of organic amnesia are not readily dissociated from deficits in attention.
Preston
G C
GC
Merck, Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Ward
C E
CE
Broks
P
P
Traub
M
M
Stahl
S M
SM
D000293:Adolescent; D000328:Adult; D001288:Attention / Q000187:drug effects*; D005260:Female; D005425:Flicker Fusion / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology*; D006801:Humans; D006993:Hypnotics and Sedatives; D008140:Lorazepam / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D014792:Visual Acuity / Q000187:drug effects
D006993:Hypnotics and Sedatives; D005442:Flumazenil; D008140:Lorazepam