Amnesic effects and subjective ratings during repeated dosing of flunitrazepam to healthy volunteers

Summary

Flunitrazepam (1 mg) or placebo was administered once daily over a treatment period of 8 days to healthy, male volunteers to study the time course of the effects on memory functions and on subjective ratings of alertness and tension. The plasma level of flunitrazepam increased by approximately 40% (P<0.05) during the treatment period. The mean pre-dose level of flunitrazepam on day 4 and day 8 was approximately 0.005 ώM, and no residual effects on memory functions were observed. Intake of flunitrazepam decreased the number of freely recalled words by about 85% (P<0.05) and significantly affected the subjects' rating of attention when tested during the first few hours after drug intake on day 1 of treatment. However, no significant effect on the subjects' rating of relaxation was observed. When tested similarly after 8 days treatment, flunitrazepam significantly affected the subjects' rating of relaxation (P<0.01). Furthermore, no tolerance developed for the effect of flunitrazepam on free recall (P>0.3) and the subjects' rating of attention (P>0.7), and these effects had nearly equal time courses during the treatment period. This may indicate that the amnesic effect of benzodiazepines is at least partially mediated through the effects on attention or general arousal. Two of the subjects in the active drug group reported adverse reactions or incidents of discomfort during the 1st week following the treatment period, whereas none in the placebo group reported such reactions.