Impairment of memory and plasma flunitrazepam levels

Abstract

Flunitrazepam was administered to volunteers in three di¤erent oral doses. The e¤ects on psychomotor sedation, attention, working memory and explicit memory were then assessed at various intervals after dosing and compared with levels of the drug in the plasma. Three groups of 12 healthy males with similar levels of education were given placebo or ßunitrazepam (1, 2 or 4 mg) in a double-blind, random-sequence study. Volunteers completed a battery of tests at night, 3.5 h after taking the drug and in the morning, 10 h afterward. Blood samples were collected for drug analysis before and after the nocturnal tests and before morning tests. At night, only the highest dose of ßunitrazepam (4 mg) induced signiÞcant changes in psychomotor sedation, attention, working memory, and prose immediate recall. Doses of 2 and 4 mg ßunitrazepam signiÞcantly reduced the mean scores of explicit memory (morning tests). Z-scores, calculated from di¤erences between ßunitrazepam and placebo, revealed that 2 mg ßunitrazepam impaired memory but not alertness or attention. Linear regression analysis of the relationship between plasma levels of ßunitrazepam and its e¤ects (Z-scores) indicated that there was a signiÞcant positive correlation between peak levels of ßunitrazepam at night and impairment of night attention and explicit memory, i.e. delayed recall of prose (r = 0.59, P < 0.01) and trigrams (r = 0.55, P < 0.01). However, memory and attention Z-scores as a function of plasma levels Þtted with nonlinear regression analysis to the E max model had higher correlation coe¦cients. To produce an e¤ect equal to 50 % of the maximum e¤ect for memory impairment, concentrations (EC 50 ) were 6.1 and 6.4 ng / ml for prose and trigrams delayed recall; but for attention they were much higher, at 13.2 ng / ml. The overall results indicate that higher concentrations were needed to impair attention than were required to impair memory.

Effects of word frequency on recall memory following lorazepam, alcohol, and lorazepam alcohol interaction in healthy volunteers

“…**P<0.01 compared with placebo Table 2 Magnitude of effect of alcohol 0.6 g/kg (ALC), lorazepam 2 mg (LOR), and lorazepam 2 mg with alcohol 0.6 g/kg (LOR+ALC) compared with placebo control, on immediate and delayed word recall for low-frequency (LF) and high-frequency (HF) words using a standardized d value (Cohen 1988 from memory (Veselis et al 1997). This concern has been allayed by showing that higher drug doses are required to impair attention than to impair memory, and that the sedative and memory impairing effects can be dissociated by the benzodiazepine antagonist, flumazenil (Hommer et al 1993;Bareggi et al 1998). In all treatment conditions, a greater proportion of HF words were recalled than LF words.…”

Melatonin Therapy: From Benzodiazepine-Dependent Insomnia to Authenticity and Autonomy

“…The inhibition of each by benzodiazepines is far too high a price to pay for sleep. [2][3][4] While benzodiazepines have a role to play in treating the acute complications of trauma (acute stress disorder) by providing relief from agitation, its potential inhibition of autobiographical and procedural memory formation and retrieval is a major roadblock in treating patients with posttraumatic stress disorder by helping those who are suffering find renewed meaning and exercise renewed skill in coping with life. 5 The alternative of using sedating antidepressants, such as trazodone, for sleep can result in dream suppression or suppressed dream recall, although overly vivid and disturbing dreams have been reported as well with other antidepressants.…”

Flunitrazepam und Fahrtüchtigkeit

“…In einer Studie wurde ein realer Fahrtest [27], in zwei ein Fahrsimulator [25,26] [27,43,45], ebenso wenig im DSST [31,46]. In Bezug auf die Aufmerksamkeitsleistung [26,38,40,43], die mit verschiedenen Verfahren untersucht wurde, liegen unterschiedliche Ergebnisse vor, wobei jedoch nur am Wiener Determinationsgerät (WDG) [43] und im Aufmerksamkeitsbelastungstest d2 [26] eine signifikante Verschlechterung im Vergleich zu Plazebo nachweisbar war. Auch die Reaktionszeit wurde mit verschiedenen Verfahren (CRT, SRT, WDG, WRG, Reaktionszeit im Informationsverarbeitungstest (IPT), Reaktionszeit auf auditive Reize) getestet [26,27,31,38,40,43,46], aber nur die Reaktionszeit im IPT [27], am WDG [43] [28,49] als auch die Leistung im CMT [40] und den Trigrammen [40] waren beeinträchtigt.…”